Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

References

1. 1.↵
   2. Dominici M,
   3. Le Blanc K,
   4. Mueller I,
   5. Slaper-Cortenbach I,
   6. Marini F,
   7. Krause D, et al.

   Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315–7.

   OpenUrlCrossRefPubMed
2. 2.↵
   2. Nwabo Kamdje AH,
   3. Mosna F,
   4. Bifari F,
   5. Lisi V,
   6. Bassi G,
   7. Malpeli G, et al.

   Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow–derived mesenchymal stromal cells. Blood. 2011; 118: 380–9.

   OpenUrlAbstract/FREE Full Text
3. 3.↵
   2. Cislo-Pakuluk A,
   3. Marycz K.

   A promising tool in retina regeneration: current perspectives and challenges when using mesenchymal progenitor stem cells in veterinary and human ophthalmological applications. Stem Cell Rev Rep. 2017; 13: 598–602.

   OpenUrl
4. 4.
   2. Luo Y,
   3. Kishi S,
   4. Sasaki T,
   5. Ohmori H,
   6. Fujiwara-Tani R,
   7. Mori S, et al.

   Targeting claudin-4 enhances chemosensitivity in breast cancer. Cancer Sci. 2020; 111: 1840–50.

   OpenUrl
5. 5.
   2. Oswald J,
   3. Boxberger S,
   4. Jørgensen B,
   5. Feldmann S,
   6. Ehninger G,
   7. Bornhäuser M, et al.

   Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 2004; 22: 377–84.

   OpenUrlCrossRefPubMedWeb of Science
6. 6.↵
   2. Xuan W,
   3. Khan M,
   4. Ashraf M.

   Extracellular vesicles from notch activated cardiac mesenchymal stem cells promote myocyte proliferation and neovasculogenesis. Front Cell Dev Biol. 2020; 8: 11. Available at: https://www.frontiersin.org/articles/10.3389/fcell.2020.00011/full

   OpenUrl
7. 7.↵
   2. Atiya H,
   3. Frisbie L,
   4. Pressimone C,
   5. Coffman L.

   Mesenchymal stem cells in the tumor microenvironment. Adv Exp Med Biol. 2020; 1234: 31–42.

   OpenUrlCrossRef
8. 8.↵
   2. Osman A,
   3. Afify SM,
   4. Hassan G,
   5. Fu X,
   6. Seno A,
   7. Seno M.

   Revisiting cancer stem cells as the origin of cancer-associated cells in the tumor microenvironment: a hypothetical view from the potential of iPSCs. Cancers (Basel). 2020; 12: 879.

   OpenUrl
9. 9.↵
   2. Nwabo Kamdje AH,
   3. Seke Etet PF,
   4. Vecchio L,
   5. Muller JM,
   6. Krampera M,
   7. Lukong KE.

   Signaling pathways in breast cancer: therapeutic targeting of the microenvironment. Cell Signal. 2014; 26: 2843–56.

   OpenUrl
10. 10.↵
    2. Seke Etet PF,
    3. Vecchio L,
    4. Bogne KP,
    5. Nukenine NE,
    6. Krampera M,
    7. Nwabo Kamdje AH.

    Normal hematopoiesis and hematologic malignancies: role of canonical Wnt signaling pathway and stromal microenvironment. Biochim Biophys Acta. 2012; 1835: 1–10.

    OpenUrl
11. 11.↵
    2. Barberini DJ,
    3. Freitas NPP,
    4. Magnoni MS,
    5. Maia L,
    6. Listoni AJ,
    7. Heckler MC, et al.

    Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential. Stem Cell Res Ther. 2014; 5: 25.

    OpenUrlPubMed
12. 12.
    2. Li C,
    3. Wu X,
    4. Tong J,
    5. Yang X,
    6. Zhao J,
    7. Zheng Q, et al.

    Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther. 2015; 6: 55.

    OpenUrlCrossRefPubMed
13. 13.↵
    2. Ying C,
    3. Zhi-bo H,
    4. Fang-yun X,
    5. You-wei W,
    6. Xiao-ming F,
    7. Fang C, et al.

    Adipogenic potentials of mesenchymal stem cells from human bone marrow, umbilical cord and adipose tissue are different. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014; 22: 588–94.

    OpenUrl
14. 14.↵
    2. Diangeng L,
    3. Nan W,
    4. Li Z,
    5. Zhu H,
    6. Bai X,
    7. Bo F, et al.

    Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor. Stem Cell Res Ther. 2013; 4: 103.

    OpenUrlCrossRefPubMed
15. 15.
    2. Ishiki Y,
    3. Ohnishi H,
    4. Muto Y,
    5. Matsumoto K,
    6. Nakamura T.

    Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo. Hepatology. 1992; 16: 1227–35.

    OpenUrlCrossRefPubMedWeb of Science
16. 16.
    2. Liu X,
    3. Chen H,
    4. Zhu W,
    5. Chen H,
    6. Hu X,
    7. Jiang Z, et al.

    Transplantation of SIRT1-engineered aged mesenchymal stem cells improves cardiac function in a rat myocardial infarction model. J Heart Lung Transplant. 2014; 33: 1083–92.

    OpenUrl
17. 17.
    2. Nan W,
    3. Rui Z,
    4. Shui-jing W,
    5. Chun-ling Z,
    6. Li-bin M,
    7. Chun-yu Z, et al.

    Vascular endothelial growth factor stimulates endothelial differentiation from mesenchymal stem cells via Rho/myocardin-related transcription factor–a signaling pathway. Int J Biochem Cell Biol. 2013; 45: 1447–56.

    OpenUrlCrossRefPubMed
18. 18.
    2. Sesia SB,
    3. Duhr R,
    4. Medeiros da Cunha C,
    5. Todorov A,
    6. Schaeren S,
    7. Padovan E, et al.

    Anti-inflammatory/tissue repair macrophages enhance the cartilage-forming capacity of human bone marrow-derived mesenchymal stromal cells. J Cell Physiol. 2015; 230: 1258–69.

    OpenUrl
19. 19.↵
    2. Windmolders S,
    3. De Boeck A,
    4. Koninckx R,
    5. Daniëls A,
    6. De Wever O,
    7. Bracke M, et al.

    Mesenchymal stem cell secreted platelet derived growth factor exerts a pro-migratory effect on resident Cardiac Atrial appendage Stem Cells. J Mol Cell Cardiol. 2014; 66: 177–88.

    OpenUrlCrossRefPubMed
20. 20.↵
    2. Gyukity-Sebestyén E,
    3. Harmati M,
    4. Dobra G,
    5. Németh IB,
    6. Mihály J,
    7. Zvara Á, et al.

    Melanoma-derived exosomes induce PD-1 overexpression and tumor progression via mesenchymal stem cell oncogenic reprogramming. Front Immunol. 2019; 10: 2459.

    OpenUrl
21. 21.
    2. Özdemir RBÖ,
    3. Özdemir AT,
    4. Sarıboyacı AE,
    5. Uysal O,
    6. Tuğlu Mİ,
    7. Kırmaz C.

    The investigation of immunomodulatory effects of adipose tissue mesenchymal stem cell educated macrophages on the CD4 T cells. Immunobiology. 2019; 224: 585–94.

    OpenUrl
22. 22.↵
    2. Rolandsson Enes S,
    3. Andersson Sjöland A,
    4. Skog I,
    5. Hansson L,
    6. Larsson H,
    7. Le Blanc K, et al.

    MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC. Sci Rep. 2016; 6: 29160.

    OpenUrlCrossRefPubMed
23. 23.↵
    2. Tsiklauri L,
    3. Werner J,
    4. Kampschulte M,
    5. Frommer KW,
    6. Berninger L,
    7. Irrgang M, et al.

    Visfatin alters the cytokine and matrix-degrading enzyme profile during osteogenic and adipogenic MSC differentiation. Osteoarthr Cartil. 2018; 26: 1225–35.

    OpenUrl
24. 24.↵
    2. Krueger TE,
    3. Thorek DLJ,
    4. Meeker AK,
    5. Isaacs JT,
    6. Brennen WN.

    Tumor-infiltrating mesenchymal stem cells: drivers of the immunosuppressive tumor microenvironment in prostate cancer? Prostate. 2019; 79: 320–30.

    OpenUrl
25. 25.↵
    2. Fernando RC,
    3. Mazzotti DR,
    4. Azevedo H,
    5. Sandes AF,
    6. Rizzatti EG,
    7. de Oliveira MB, et al.

    Transcriptome analysis of mesenchymal stem cells from multiple myeloma patients reveals downregulation of genes involved in cell cycle progression, immune response, and bone metabolism. Sci Rep. 2019; 9: 1056.

    OpenUrl
26. 26.↵
    2. Sarhan D,
    3. Wang J,
    4. Arvindam US,
    5. Hallstrom C,
    6. Verneris MR,
    7. Grzywacz B, et al.

    Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function. JCI Insight. 2020; 5: e130155. Available at: https://insight.jci.org/articles/view/130155
27. 27.↵
    2. Yichen C,
    3. Xi W,
    4. Juan F,
    5. Jingjing S,
    6. Da M,
    7. Liqun L, et al.

    Mesenchymal stem cells participate in oral mucosa carcinogenesis by regulating T cell proliferation. Clin Immunol. 2018; 198: 46–53.

    OpenUrl
28. 28.↵
    2. Cheng J,
    3. Li Y,
    4. Liu S,
    5. Jiang Y,
    6. Ma J,
    7. Wan L, et al.

    CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway. FASEB J. 2019; 33: 4755–64.

    OpenUrl
29. 29.↵
    2. Salminen A,
    3. Kaarniranta K,
    4. Kauppinen A.

    ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease. J Mol Med (Berl). 2020; 98: 633–50.

    OpenUrl
30. 30.↵
    2. Thomas R,
    3. Wang W,
    4. Su D-M.

    Contributions of age-related thymic involution to immunosenescence and inflammaging. Immun Ageing. 2020; 17: 2.

    OpenUrl
31. 31.↵
    2. Shen Y,
    3. Xue C,
    4. Li X,
    5. Ba L,
    6. Gu J,
    7. Sun Z, et al.

    Effects of gastric cancer cell-derived exosomes on the immune regulation of mesenchymal stem cells by the NF-kB signaling pathway. Stem Cells Dev. 2019; 28: 464–76.

    OpenUrl
32. 32.↵
    2. Abdul-Aziz AM,
    3. Sun Y,
    4. Hellmich C,
    5. Marlein CR,
    6. Mistry J,
    7. Forde E, et al.

    Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment. Blood. 2019; 133: 446–56.

    OpenUrlAbstract/FREE Full Text
33. 33.↵
    2. Jafarzadeh N,
    3. Safari Z,
    4. Pornour M,
    5. Amirizadeh N,
    6. Forouzandeh Moghadam M,
    7. Sadeghizadeh M.

    Alteration of cellular and immune-related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes. J Cell Physiol. 2019; 234: 3697–710.

    OpenUrl
34. 34.↵
    2. Al-Khalaf HH,
    3. Ghebeh H,
    4. Inass R,
    5. Aboussekhra A.

    Senescent breast luminal cells promote carcinogenesis through interleukin-8-dependent activation of stromal fibroblasts. Mol Cell Biol. 2019; 39: e00359–18. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321881/
35. 35.↵
    2. Shi L,
    3. Zhao Y,
    4. Fei C,
    5. Guo J,
    6. Jia Y,
    7. Wu D, et al.

    Cellular senescence induced by S100A9 in mesenchymal stromal cells through NLRP3 inflammasome activation. Aging (Albany NY). 2019; 11: 9626–42.

    OpenUrl
36. 36.↵
    2. Giallongo C,
    3. Tibullo D,
    4. Camiolo G,
    5. Parrinello NL,
    6. Romano A,
    7. Puglisi F, et al.

    Correction: TLR4 signaling drives mesenchymal stromal cells commitment to promote tumor microenvironment transformation in multiple myeloma. Cell Death Dis. 2019; 10: 820.

    OpenUrl
37. 37.↵
    2. Walsh HR,
    3. Cruickshank BM,
    4. Brown JM,
    5. Marcato P.

    The flick of a switch: conferring survival advantage to breast cancer stem cells through metabolic plasticity. Front Oncol. 2019; 9: 753. Available at: https://www.frontiersin.org/articles/10.3389/fonc.2019.00753/full

    OpenUrl
38. 38.↵
    2. Akella NM,
    3. Minh GL,
    4. Ciraku L,
    5. Mukherjee A,
    6. Bacigalupa ZA,
    7. Mukhopadhyay D, et al.

    O-GlcNAc transferase regulates cancer stem-like potential of breast cancer cells. Mol Cancer Res. 2020; 18: 585–98.

    OpenUrlAbstract/FREE Full Text
39. 39.↵
    2. Yang J,
    3. Ren B,
    4. Yang G,
    5. Wang H,
    6. Chen G,
    7. You L, et al.

    The enhancement of glycolysis regulates pancreatic cancer metastasis. Cell Mol Life Sci. 2020; 77: 305–21.

    OpenUrl
40. 40.↵
    2. Chandra A,
    3. Jahangiri A,
    4. Chen W,
    5. Nguyen AT,
    6. Yagnik G,
    7. Pereira MP, et al.

    Clonal ZEB1-driven mesenchymal transition promotes targetable oncologic anti-angiogenic therapy resistance. Cancer Res. 2020; 80: 1498–511. Available at: https://cancerres.aacrjournals.org/content/early/2020/02/08/0008-5472.CAN-19-1305

    OpenUrlAbstract/FREE Full Text
41. 41.↵
    2. Ma Z,
    3. Cui X,
    4. Lu L,
    5. Chen G,
    6. Yang Y,
    7. Hu Y, et al.

    Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis. Stem Cell Res Ther. 2019; 10: 60.

    OpenUrl
42. 42.↵
    2. Lung DK,
    3. Warrick JW,
    4. Hematti P,
    5. Callander NS,
    6. Mark CJ,
    7. Miyamoto S, et al.

    Bone marrow stromal cells transcriptionally repress ESR1 but cannot overcome constitutive ESR1 mutant activity. Endocrinology. 2019; 160: 2427–40.

    OpenUrl
43. 43.↵
    2. Schmohl KA,
    3. Mueller AM,
    4. Dohmann M,
    5. Spellerberg R,
    6. Urnauer S,
    7. Schwenk N, et al.

    Integrin αvβ3-mediated effects of thyroid hormones on mesenchymal stem cells in tumor angiogenesis. Thyroid. 2019; 29: 1843–57.

    OpenUrl
44. 44.↵
    2. An J,
    3. Du Y,
    4. Fan X,
    5. Wang Y,
    6. Ivan C,
    7. Zhang XG, et al.

    EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis. Oncogene. 2019; 38: 2123–34.

    OpenUrl
45. 45.↵
    2. Su S,
    3. Chen J,
    4. Yao H,
    5. Liu J,
    6. Yu S,
    7. Lao L, et al.

    CD10+GPR77+ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell. 2018; 172: 841–56.e16.

    OpenUrlCrossRefPubMed
46. 46.↵
    2. Qiong W,
    3. Yu-Chao Z,
    4. Li-Fan Z,
    5. Pan L,
    6. Yu M,
    7. Wei-Li S, et al.

    Heat shock factor 1 in cancer-associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma. Cancer Sci. 2019; 110: 1790–803.

    OpenUrl
47. 47.↵
    2. Du Y,
    3. Shao H,
    4. Moller M,
    5. Prokupets R,
    6. Tse YT,
    7. Liu Z.

    Intracellular Notch1 signaling in cancer-associated fibroblasts dictates the plasticity and stemness of melanoma stem/initiating cells. Stem Cells. 2019; 37: 865–75.

    OpenUrl
48. 48.↵
    2. Ligorio M,
    3. Sil S,
    4. Malagon-Lopez J,
    5. Nieman LT,
    6. Misale S,
    7. Di Pilato M, et al.

    Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer. Cell. 2019; 178: 160–175.e27.

    OpenUrlCrossRef
49. 49.↵
    2. Chikina AS,
    3. Rubtsova SN,
    4. Lomakina ME,
    5. Potashnikova DM,
    6. Vorobjev IA,
    7. Alexandrova AY.

    Transition from mesenchymal to bleb-based motility is predominantly exhibited by CD133-positive subpopulation of fibrosarcoma cells. Biol Cell. 2019; 111: 245–61.

    OpenUrlCrossRef
50. 50.↵
    2. Baghban R,
    3. Roshangar L,
    4. Jahanban-Esfahlan R,
    5. Seidi K,
    6. Ebrahimi-Kalan A,
    7. Jaymand M, et al.

    Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020; 18: 59.

    OpenUrlCrossRef
51. 51.↵
    2. Bussard KM,
    3. Mutkus L,
    4. Stumpf K,
    5. Gomez-Manzano C,
    6. Marini FC.

    Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res. 2016;18. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982339/
52. 52.↵
    2. Zhan Y,
    3. Wang L,
    4. Liu G,
    5. Zhang X,
    6. Yang J,
    7. Pan Y, et al.

    The reparative effects of human adipose-derived mesenchymal stem cells in the chemotherapy-damaged thymus. Stem Cells Dev. 2018; 28: 186–95.

    OpenUrl
53. 53.↵
    2. François S,
    3. Usunier B,
    4. Forgue-Lafitte M-E,
    5. L’Homme B,
    6. Benderitter M,
    7. Douay L, et al.

    Mesenchymal stem cell administration attenuates colon cancer progression by modulating the immune component within the colorectal tumor microenvironment. Stem Cells Transl Med. 2019; 8: 285–300.

    OpenUrl
54. 54.↵
    2. Wang B,
    3. Wu ZH,
    4. Lou PY,
    5. Chai C,
    6. Han SY,
    7. Ning JF, et al.

    Human bone marrow-derived mesenchymal stem cell-secreted exosomes overexpressing microRNA-34a ameliorate glioblastoma development via down-regulating MYCN. Cell Oncol. 2019; 42: 783–99.

    OpenUrl
55. 55.↵
    2. Xia C,
    3. Wang T,
    4. Cheng H,
    5. Dong Y,
    6. Weng Q,
    7. Sun G, et al.

    Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment. Leukemia. 2020; 1–9: 2375–83.

    OpenUrl
56. 56.↵
    2. Liu Y,
    3. Ren H,
    4. Zhou Y,
    5. Shang L,
    6. Zhang Y,
    7. Yang F, et al.

    The hypoxia conditioned mesenchymal stem cells promote hepatocellular carcinoma progression through YAP mediated lipogenesis reprogramming. J Exp Clin Cancer Res. 2019; 38: 228.

    OpenUrl
57. 57.↵
    2. Bu L,
    3. Baba H,
    4. Yoshida N,
    5. Miyake K,
    6. Yasuda T,
    7. Uchihara T, et al.

    Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment. Oncogene. 2019; 38: 4887–901.

    OpenUrlCrossRef
58. 58.↵
    2. Tew BY,
    3. Legendre C,
    4. Gooden GC,
    5. Johnson KN,
    6. Martinez RA,
    7. Kiefer J, et al.

    Isolation and characterization of patient-derived CNS metastasis-associated stromal cell lines. Oncogene. 2019; 38: 4002–14.

    OpenUrl
59. 59.↵
    2. Mizutani Y,
    3. Kobayashi H,
    4. Iida T,
    5. Asai N,
    6. Masamune A,
    7. Hara A, et al.

    Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis. Cancer Res. 2019; 79: 5367–81.

    OpenUrlAbstract/FREE Full Text
60. 60.↵
    2. García-Hernández M de la L,
    3. Uribe-Uribe NO,
    4. Espinosa-González R,
    5. Kast WM,
    6. Khader SA,
    7. Rangel-Moreno J.

    A unique cellular and molecular microenvironment is present in tertiary lymphoid organs of patients with spontaneous prostate cancer regression. Front Immunol. 2017; 8: 563. Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2017.00563/full

    OpenUrl
61. 61.↵
    2. Pelizzo G,
    3. Veschi V,
    4. Mantelli M,
    5. Croce S,
    6. Benedetto VD,
    7. D’Angelo P, et al.

    Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells. BMC Cancer. 2018; 18: 1176. Available at: https://moh-it.pure.elsevier.com/en/publications/microenvironment-in-neuroblastoma-isolation-and-characterization

    OpenUrlCrossRefPubMed
62. 62.↵
    2. Coffman LG,
    3. Pearson AT,
    4. Frisbie LG,
    5. Freeman Z,
    6. Christie E,
    7. Bowtell DD, et al.

    Ovarian carcinoma-associated mesenchymal stem cells arise from tissue-specific normal stroma. Stem Cells. 2018; 37: 257–69.

    OpenUrl
63. 63.↵
    2. Wörner PM,
    3. Schächtele DJ,
    4. Barabadi Z,
    5. Srivastav S,
    6. Chandrasekar B,
    7. Izadpanah R, et al.

    Breast tumor microenvironment can transform naive mesenchymal stem cells into tumor-forming cells in nude mice. Stem Cells Dev. 2018; 28: 341–52.

    OpenUrl
64. 64.↵
    2. Casagrande N,
    3. Borghese C,
    4. Visser L,
    5. Mongiat M,
    6. Colombatti A,
    7. Aldinucci D.

    CCR5 antagonism by maraviroc inhibits Hodgkin lymphoma microenvironment interactions and xenograft growth. Haematologica. 2019; 104: 564–75.

    OpenUrlAbstract/FREE Full Text
65. 65.↵
    2. Rut T,
    3. Yong H,
    4. Igor K,
    5. Michael K,
    6. Jung-Yi L,
    7. Jessica T-G, et al.

    Gene signatures of quiescent glioblastoma cells reveal mesenchymal shift and interactions with niche microenvironment. EBioMedicine. 2019; 42: 252–69.

    OpenUrl
66. 66.↵
    2. Yeela S,
    3. Dalia CA,
    4. Zohar Y,
    5. Karl S,
    6. Maty T.

    Reciprocal reprogramming of cancer cells and associated mesenchymal stem cells in gastric cancer. Stem Cells. 2018; 37: 176–89.

    OpenUrl
67. 67.↵
    2. Hughes RM,
    3. Simons BW,
    4. Khan H,
    5. Miller R,
    6. Kugler V,
    7. Torquato S, et al.

    Asporin restricts mesenchymal stromal cell differentiation, alters the tumor microenvironment, and drives metastatic progression. Cancer Res. 2019; 79: 3636–50.

    OpenUrlCrossRef
68. 68.↵
    2. Ikeda T,
    3. Nishita M,
    4. Hoshi K,
    5. Honda T,
    6. Kakeji Y,
    7. Minami Y.

    Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1. Cancer Sci. 2020; 111: 1254–65.

    OpenUrlCrossRef
69. 69.↵
    2. Dabbah M,
    3. Jarchowsky-Dolberg O,
    4. Attar-Schneider O,
    5. Tartakover Matalon S,
    6. Pasmanik-Chor M,
    7. Drucker L, et al.

    Multiple myeloma BM-MSCs increase the tumorigenicity of MM cells via transfer of VLA4-enriched microvesicles. Carcinogenesis. 2020; 41: 100–10.

    OpenUrl
70. 70.↵
    2. Umakoshi M,
    3. Takahashi S,
    4. Itoh G,
    5. Kuriyama S,
    6. Sasaki Y,
    7. Yanagihara K, et al.

    Macrophage-mediated transfer of cancer-derived components to stromal cells contributes to establishment of a pro-tumor microenvironment. Oncogene. 2019; 38: 2162–76.

    OpenUrl
71. 71.↵
    2. Yongchun Z,
    3. Jian-Hong Z,
    4. Fu-Sheng G,
    5. Jun X.

    MiR-141-3p suppresses gastric cancer induced transition of normal fibroblast and BMSC to cancer-associated fibroblasts via targeting STAT4. Exp Mol Pathol. 2018; 107: 85–94.

    OpenUrl
72. 72.↵
    2. Guo L,
    3. Sun C,
    4. Xu S,
    5. Xu Y,
    6. Dong Q,
    7. Zhang L, et al.

    Knockdown of long non-coding RNA linc-ITGB1 inhibits cancer stemness and epithelial-mesenchymal transition by reducing the expression of Snail in non-small cell lung cancer. Thorac Cancer. 2019; 10: 128–36.

    OpenUrl
73. 73.↵
    2. Ibraheem A,
    3. Attar-Schneider O,
    4. Dabbah M,
    5. Jarchowsky OD,
    6. Matalon ST,
    7. Lishner M, et al.

    BM-MSCs-derived ECM modifies multiple myeloma phenotype and drug response in a source-dependent manner. Transl Res. 2019; 207: 83–95.

    OpenUrl
74. 74.↵
    2. Zannoni J,
    3. Mauz N,
    4. Seyve L,
    5. Meunier M,
    6. Pernet-Gallay K,
    7. Brault J, et al.

    Tumor microenvironment and clonal monocytes from chronic myelomonocytic leukemia induce a procoagulant climate. Blood Adv. 2019; 3: 1868–80.

    OpenUrlAbstract/FREE Full Text
75. 75.↵
    2. Verma D,
    3. Zanetti C,
    4. Godavarthy PS,
    5. Kumar R,
    6. Minciacchi VR,
    7. Pfeiffer J, et al.

    Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia. Leukemia. 2020; 34: 1540–52.

    OpenUrlPubMed
76. 76.↵
    2. Ghosh D,
    3. Mejia Pena C,
    4. Quach N,
    5. Xuan B,
    6. Lee AH,
    7. Dawson MR.

    Senescent mesenchymal stem cells remodel extracellular matrix driving breast cancer cells to a more-invasive phenotype. J Cell Sci. 2020; 133: jcs232470.

    OpenUrlAbstract/FREE Full Text
77. 77.↵
    2. Hwang HJ,
    3. Oh M-S,
    4. Lee DW,
    5. Kuh H-J.

    Multiplex quantitative analysis of stroma-mediated cancer cell invasion, matrix remodeling, and drug response in a 3D co-culture model of pancreatic tumor spheroids and stellate cells. J Exp Clin Cancer Res. 2019; 38: 258.

    OpenUrl
78. 78.↵
    2. Maliszewska-Olejniczak K,
    3. Brodaczewska KK,
    4. Bielecka ZF,
    5. Solarek W,
    6. Kornakiewicz A,
    7. Szczylik C, et al.

    Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells. Cytotechnology. 2019; 71: 149–63.

    OpenUrl
79. 79.↵
    2. Mazza G,
    3. Telese A,
    4. Al-Akkad W,
    5. Frenguelli L,
    6. Levi A,
    7. Marrali M, et al.

    Cirrhotic human liver extracellular matrix 3D scaffolds promote smad-dependent TGF-β1 epithelial mesenchymal transition. Cells. 2020; 9: 83.

    OpenUrl
80. 80.↵
    2. Oh I-R,
    3. Raymundo B,
    4. Kim M,
    5. Kim C-W.

    Mesenchymal stem cells co-cultured with colorectal cancer cells showed increased invasive and proliferative abilities due to its altered p53/TGF-β1 levels. Biosci Biotechnol Biochem. 2020; 84: 256–67.

    OpenUrl
81. 81.↵
    2. Tan H-X,
    3. Cao Z-B,
    4. He T-T,
    5. Huang T,
    6. Xiang C-L,
    7. Liu Y.

    TGFβ1 is essential for MSCs-CAFs differentiation and promotes HCT116 cells migration and invasion via JAK/STAT3 signaling. Onco Targets Ther. 2019; 12: 5323–34.

    OpenUrl
82. 82.↵
    2. Melzer C,
    3. von der Ohe J,
    4. Otterbein H,
    5. Ungefroren H,
    6. Hass R.

    Changes in uPA, PAI-1, and TGF-β production during breast cancer cell interaction with human mesenchymal stroma/stem-like cells (MSC). Int J Mol Sci [Internet]. 2019; 20: 2630. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600334/

    OpenUrl
83. 83.↵
    2. Balamurugan K.

    HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 2016; 138: 1058–66.

    OpenUrlCrossRefPubMed
84. 84.↵
    2. Shi Y,
    3. Wang Y,
    4. Li Q,
    5. Liu K,
    6. Hou J,
    7. Shao C, et al.

    Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol. 2018; 14: 493–507.

    OpenUrlCrossRefPubMed
85. 85.↵
    2. Cao J,
    3. Li J,
    4. Sun L,
    5. Qin T,
    6. Xiao Y,
    7. Chen K, et al.

    Hypoxia-driven paracrine osteopontin/integrin αvβ3 signaling promotes pancreatic cancer cell epithelial-mesenchymal transition and cancer stem cell-like properties by modulating forkhead box protein M1. Mol Oncol. 2019; 13: 228–45.

    OpenUrl
86. 86.↵
    2. Lin S,
    3. Zhu B,
    4. Huang G,
    5. Zeng Q,
    6. Wang C.

    Microvesicles derived from human bone marrow mesenchymal stem cells promote U2OS cell growth under hypoxia: the role of PI3K/AKT and HIF-1α. Human Cell. 2019; 32: 64–74.

    OpenUrl
87. 87.↵
    2. Li-Na Z,
    3. Ying-Hui H,
    4. Lei Z.

    Fusion of macrophages promotes breast cancer cell proliferation, migration and invasion through activating epithelial-mesenchymal transition and Wnt/β-catenin signaling pathway. Arch Biochem Biophys. 2019; 676: 108137.

    OpenUrl
88. 88.↵
    2. Zhang X,
    3. Sai B,
    4. Wang F,
    5. Wang L,
    6. Wang Y,
    7. Zheng L, et al.

    Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT. Mol Cancer. 2019; 18: 40.

    OpenUrl
89. 89.↵
    2. Daniel SK,
    3. Sullivan KM,
    4. Labadie KP,
    5. Pillarisetty VG.

    Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma. Clin Transl Med. 2019; 8: 10.

    OpenUrl
90. 90.↵
    2. Garcés J-J,
    3. Simicek M,
    4. Vicari M,
    5. Brozova L,
    6. Burgos L,
    7. Bezdekova R, et al.

    Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination. Leukemia. 2020; 34: 589–603.

    OpenUrl
91. 91.↵
    2. Yue-Lei C,
    3. Yihe Z,
    4. Junwen W,
    5. Na C,
    6. Weiying F,
    7. Jianing Z, et al.

    A 17 gene panel for non-small-cell lung cancer prognosis identified through integrative epigenomic-transcriptomic analyses of hypoxia-induced epithelial-mesenchymal transition. Mol Oncol. 2019; 13: 1490–502.

    OpenUrl
92. 92.↵
    2. Kang N,
    3. Choi SY,
    4. Kim BN,
    5. Yeo CD,
    6. Park CK,
    7. Kim YK, et al.

    Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation. BMC Cancer. 2019; 19: 148. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375212/

    OpenUrl
93. 93.↵
    2. Chen S,
    3. Zhang J,
    4. Chen J,
    5. Wang Y,
    6. Zhou S,
    7. Huang L, et al.

    RER1 enhances carcinogenesis and stemness of pancreatic cancer under hypoxic environment. J Exp Clin Cancer Res. 2019; 38: 15.

    OpenUrlCrossRef
94. 94.↵
    2. Torres Á,
    3. Erices JI,
    4. Sanchez F,
    5. Ehrenfeld P,
    6. Turchi L,
    7. Virolle T, et al.

    Extracellular adenosine promotes cell migration/invasion of Glioblastoma Stem-like Cells through A3 Adenosine Receptor activation under hypoxia. Cancer Lett. 2019; 446: 112–22.

    OpenUrl
95. 95.↵
    2. Bauer J,
    3. Emon MAB,
    4. Staudacher JJ,
    5. Thomas AL,
    6. Zessner-Spitzenberg J,
    7. Mancinelli G, et al.

    Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling. Sci Rep. 2020; 10: 50.

    OpenUrlCrossRef
96. 96.↵
    2. Saforo D,
    3. Omer L,
    4. Smolenkov A,
    5. Barve A,
    6. Casson L,
    7. Boyd N, et al.

    Primary lung cancer samples cultured under microenvironment-mimetic conditions enrich for mesenchymal stem-like cells that promote metastasis. Sci Rep. 2019; 9: 4177.

    OpenUrl
97. 97.↵
    2. Iyengar NM,
    3. Gucalp A,
    4. Dannenberg AJ,
    5. Hudis CA.

    Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol. 2016; 34: 4270–6.

    OpenUrlPubMed
98. 98.
    2. Park J,
    3. Morley TS,
    4. Kim M,
    5. Clegg DJ,
    6. Scherer PE.

    Obesity and cancer mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol. 2014; 10: 455–65.

    OpenUrlCrossRefPubMed
99. 99.↵
    2. Quail DF,
    3. Dannenberg AJ.

    The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019; 15: 139–54.

    OpenUrl
100. 100.↵
     2. Su F,
     3. Ahn S,
     4. Saha A,
     5. DiGiovanni J,
     6. Kolonin MG.

     Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance. Oncogene. 2019; 38: 1979–88.

     OpenUrl
101. 101.↵
     2. Wu S,
     3. Wang Y,
     4. Yuan Z,
     5. Wang S,
     6. Du H,
     7. Liu X, et al.

     Human adipose-derived mesenchymal stem cells promote breast cancer MCF7 cell epithelial-mesenchymal transition by cross interacting with the TGF-β/Smad and PI3K/AKT signaling pathways. Mol Med Rep. 2019; 19: 177–86.

     OpenUrl
102. 102.↵
     2. Berlier JL,
     3. Rethnam M,
     4. Banu Binte Abdul Majeed A,
     5. Suda T.

     Modification of the bone marrow MSC population in a xenograft model of early multiple myeloma. Biochem Biophys Res Commun. 2019; 508: 1175–81.

     OpenUrl
103. 103.↵
     2. Goralski KB,
     3. Jackson AE,
     4. McKeown BT,
     5. Sinal CJ.

     More than an adipokine: the complex roles of chemerin signaling in cancer. Int J Mol Sci. 2019; 20: 4778.

     OpenUrl
104. 104.↵
     2. Poggi A,
     3. Varesano S,
     4. Zocchi MR.

     How to hit mesenchymal stromal cells and make the tumor microenvironment immunostimulant rather than immunosuppressive. Front Immunol. 2018; 9: 262. Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2018.00262/full

     OpenUrl
105. 105.↵
     2. Turley SJ,
     3. Cremasco V,
     4. Astarita JL.

     Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol. 2015; 15: 669–82.

     OpenUrlCrossRefPubMed
106. 106.↵
     2. Al-Jawadi A,
     3. Rasha F,
     4. Ramalingam L,
     5. Alhaj S,
     6. Moussa H,
     7. Gollahon L, et al.

     Protective effects of eicosapentaenoic acid in adipocyte-breast cancer cell cross talk. J Nutr Biochem. 2020; 75: 108244.

     OpenUrl
107. 107.↵
     2. Mandal S,
     3. Arfuso F,
     4. Sethi G,
     5. Dharmarajan A,
     6. Warrier S.

     Encapsulated human mesenchymal stem cells (eMSCs) as a novel anti-cancer agent targeting breast cancer stem cells: development of 3D primed therapeutic MSCs. Int J Biochem Cell Biol. 2019; 110: 59–69.

     OpenUrl
108. 108.↵
     2. Kato M,
     3. Placencio-Hickok VR,
     4. Madhav A,
     5. Haldar S,
     6. Tripathi M,
     7. Billet S, et al.

     Heterogeneous cancer-associated fibroblast population potentiates neuroendocrine differentiation and castrate resistance in a CD105-dependent manner. Oncogene. 2019; 38: 716–30.

     OpenUrlCrossRef
109. 109.
     2. Rogers O,
     3. Yen H,
     4. Solomon A,
     5. Drake C,
     6. Denmeade SR.

     An IL-2 proaerolysin fusion toxin that selectively eliminates regulatory t cells to enhance antitumor immune response. The Prostate. 2019; 79: 1071–8.

     OpenUrl
110. 110.↵
     2. Cao W,
     3. Liu B,
     4. Xia F,
     5. Duan M,
     6. Hong Y,
     7. Niu J, et al.

     MnO2@Ce6-loaded mesenchymal stem cells as an “oxygen-laden guided-missile” for the enhanced photodynamic therapy on lung cancer. Nanoscale. 2020; 12: 3090–102.

     OpenUrl
111. 111.
     2. Wang X,
     3. Chen H,
     4. Zeng X,
     5. Guo W,
     6. Jin Y,
     7. Wang S, et al.

     Efficient lung cancer-targeted drug delivery via a nanoparticle/MSC system. Acta Pharmaceutica Sinica B. 2019; 9: 167–76.

     OpenUrl
112. 112.
     2. Mahasa KJ,
     3. Pillis L de,
     4. Ouifki R,
     5. Eladdadi A,
     6. Maini P,
     7. Yoon AR, et al.

     Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy. Sci Rep. 2020; 10: 425.

     OpenUrlPubMed
113. 113.
     2. Mohamed Y,
     3. Mohamed Y,
     4. Elsayed S,
     5. Gazia M,
     6. Abdel-Aleem G,
     7. Shafik N, et al.

     Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC. Biomed Pharmacother. 2019; 114: 108732.

     OpenUrl
114. 114.↵
     2. Yang J,
     3. Lv K,
     4. Sun J,
     5. Guan J.

     Anti-tumor effects of engineered mesenchymal stem cells in colon cancer model [Internet]. Cancer Manag Res. 2019; 11: 8443–50.

     OpenUrl
115. 115.↵
     2. Kim SD,
     3. Yi JM,
     4. Park M-T.

     Irradiated endothelial cells modulate the malignancy of liver cancer cells. Oncol Lett. 2019; 17: 2187–96.

     OpenUrl
116. 116.↵
     2. Boada M,
     3. Echarte L,
     4. Guillermo C,
     5. Diaz L,
     6. Touriño C,
     7. Grille S.

     5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients. Hematol Transfus Cell Ther. 2020; http://www.sciencedirect.com/science/article/pii/S2531137920300043 In press.
117. 117.↵
     2. Olga OU,
     3. Olga VZ,
     4. Maria IE,
     5. Irina VO,
     6. Elena RA,
     7. Ludmila BB, et al.

     Low-dose photodynamic therapy promotes angiogenic potential and increases immunogenicity of human mesenchymal stromal cells. J Photochem Photobiol B. 2019; 199: 111596.

     OpenUrl
118. 118.↵
     2. Costea T,
     3. Vlad OC,
     4. Miclea L-C,
     5. Ganea C,
     6. Szöllősi J,
     7. Mocanu M-M.

     Alleviation of multidrug resistance by flavonoid and non-flavonoid compounds in breast, lung, colorectal and prostate cancer. Int J Mol Sci. 2020; 21: 401.

     OpenUrl
119. 119.↵
     2. Maj M,
     3. Kokocha A,
     4. Bajek A,
     5. Drewa T.

     The effects of adipose-derived stem cells on CD133-expressing bladder cancer cells. J Cell Biochem. 2019; 120: 11562–72.

     OpenUrl
120. 120.↵
     2. Blache U,
     3. Horton ER,
     4. Xia T,
     5. Schoof EM,
     6. Blicher LH,
     7. Schönenberger A, et al.

     Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments. Life Sci All. 2019; 2: e201900304.
121. 121.↵
     2. Quach ND,
     3. Kaur SP,
     4. Eggert MW,
     5. Ingram L,
     6. Ghosh D,
     7. Sheth S, et al.

     Paradoxical role of glypican-1 in prostate cancer cell and tumor growth. Sci Rep. 2019; 9: 11478.

     OpenUrl
122. 122.↵
     2. Kopantzev EP,
     3. Kopantseva MR,
     4. Grankina EV,
     5. Mikaelyan A,
     6. Egorov VI,
     7. Sverdlov ED.

     Activation of IGF/IGF-IR signaling pathway fails to induce epithelial-mesenchymal transition in pancreatic cancer cells. Pancreatology. 2019; 19: 390–6.

     OpenUrl
123. 123.↵
     2. Zhou X,
     3. Li T,
     4. Chen Y,
     5. Zhang N,
     6. Wang P,
     7. Liang Y, et al.

     Mesenchymal stem cell-derived extracellular vesicles promote the in vitro proliferation and migration of breast cancer cells through the activation of the ERK pathway. Int J Oncol. 2019; 54: 1843–52.

     OpenUrl
124. 124.↵
     2. Ritter A,
     3. Friemel A,
     4. Roth S,
     5. Kreis NN,
     6. Hoock SC,
     7. Safdar BK, et al.

     Subcutaneous and visceral adipose-derived mesenchymal stem cells: commonality and diversity. Cells. 2019; 8: 1288.

     OpenUrl
125. 125.↵
     2. Huang Y,
     3. Li Q,
     4. Zhang K,
     5. Hu M,
     6. Wang Y,
     7. Du L, et al.

     Single cell transcriptomic analysis of human mesenchymal stem cells reveals limited heterogeneity. Cell Death Dis. 2019; 10: 1–12.

     OpenUrlCrossRefPubMed