RT Journal Article
SR Electronic
T1 CD44v8-10 is a marker for malignant traits and a potential driver of bone metastasis in a subpopulation of prostate cancer cells
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 788
OP 807
DO 10.20892/j.issn.2095-3941.2020.0495
VO 18
IS 3
A1 Rosaria A. Fontanella
A1 Silvia Sideri
A1 Chiara Di Stefano
A1 Angiolina Catizone
A1 Silvia Di Agostino
A1 Daniela F. Angelini
A1 Gisella Guerrera
A1 Luca Battistini
A1 Giulia Battafarano
A1 Andrea Del Fattore
A1 Antonio Francesco Campese
A1 Fabrizio Padula
A1 Paola De Cesaris
A1 Antonio Filippini
A1 Anna Riccioli
YR 2021
UL http://www.cancerbiomed.org/content/18/3/788.abstract
AB Objective: Bone metastasis is a clinically important outcome of prostate carcinoma (PC). We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell line. These cells, originated from the spontaneous conversion of a CD44-negative subpopulation, stably express the CD44v8-10 isoform (CD44v8-10pos) and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44v8-10 silencing.Methods: Flow cytometry, enzyme-linked immunoassay, immunofluorescence, and Western blot were used for phenotypic and immunologic characterization. Real-time quantitative polymerase chain reaction and functional assays were used to assess osteomimicry.Results: Analysis of epithelial–mesenchymal transition markers showed that CD44v8-10pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry, acquiring bone cell phenotypic and behavioral traits. Use of specific siRNA evidenced the ability of CD44v8-10 variant to confer osteomimetic features, hence the potential to form bone-specific metastasis. Moreover, the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a tumor. Here we report that CD44v8-10pos cells express programmed death ligand 1, a negative regulator of anticancer immunity, and secrete exceptionally high amounts of interleukin-6, favoring osteoclastogenesis and immunosuppression in bone microenvironment. Notably, we identified a novel pathway activated by CD44v8-10, involving tafazzin (TAZ) and likely the Wnt/TAZ axis, known to play a role in upregulating osteomimetic genes.Conclusions: CD44v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone. A novel link between TAZ and CD44v8-10 is also shown.