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Molecular plasticity of human melanoma cells

Oncogene volume 22, pages 3070–3075 (2003)Cite this article

Abstract

The molecular analysis of tumors, such as melanoma, has benefited significantly from microarray technology that can facilitate the classification of tumors based on the differential expression of genes. The data summarized in this review describe the molecular profile of aggressive cutaneous and uveal melanoma cells as that of multiple phenotypes similar to a pluripotent, embryonic-like stem cell. A noteworthy example of the plasticity of the aggressive melanoma cell phenotype is demonstrated by the ability of these tumor cells to engage in vasculogenic mimicry and neovascularization. A review of the current evidence demonstrating important cellular and molecular determinants of melanoma vasculogenic mimicry is presented. In addition, novel signaling pathways are discussed, involving VE-cadherin, EphA2, FAK, and PI 3-kinase, which promote cell migration, invasion, and matrix remodeling. The observations summarized in this review describe some of the key molecular events that regulate the process of melanoma vasculogenic mimicry and identify new signal transduction pathways that can serve as putative targets for therapeutic intervention.

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References

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO and Staudt LM . (2000). Nature, 403, 503–511.

  • Bayless KJ and Davis GE . (2002). J. Cell Sci., 115, 1123–1136.

  • Bazzoni G, Dejana E and Lampugnani MG . (1999). Curr. Opin. Cell Biol., 11, 573–581.

  • Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V, Hayward N and Trent J . (2000). Nature, 406, 536–540.

  • Carmeliet P, Lampugnani M-G, Moons L, Brevierio F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert J-M, Collen D and Dejana E (1999). Cell, 98, 147–157.

  • Carmeliet P . (2000). Nat. Med., 6, 389–395.

  • Chan TO, Rodeck U, Chan AM, Kimmelman AC, Rittenhouse SE, Panayotou G and Tsichlis PN . (2002). Cancer Cell, 1, 181–191.

  • Clarijs R, Otte-Höller, Ruiter DJ and de Wall RMW . (2002). Invest. Ophthalmol. Vis. Sci., 43, 912–918.

  • Colognato H and Yurchenco PD . (2000). Dev. Dynam., 218, 213–234.

  • D'Amour KA and Gage FH . (2002). Nat. Med., 8, 213–214.

  • Folberg R, Hendrix MJC and Maniotis AJ . (2000). Am. J. Pathol., 156, 361–381.

  • Folkman J . (1995). N. Engl. J. Med., 333, 1757–1763.

  • Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG and Quaranta V . (1997). Science, 277, 225–228.

  • Gumbiner BM . (1996). Cell, 4, 345–357.

  • Hendrix MJC, Seftor EA, Meltzer PS, Gardner LMG, Hess AR, Kirschmann DA, Schatteman GC and Seftor REB . (2001). Proc. Natl. Acad. Sci. USA, 98, 8018–8023.

  • Hendrix MJC, Seftor REB, Seftor EA, Gruman LM, Lee LML, Nickoloff BJ, Miele L, Sheriff D and Schatteman GC . (2002). Cancer Res., 62, 665–668.

  • Hess AR . (2002). Dissertation, pp. 1–150. The University of Iowa, Iowa City, Iowa.

  • Hess AR, Seftor EA, Gardner LMG, Carles-Kinch K, Schneider GB, Seftor REB, Kinch MS and Hendrix MJC . (2001). Cancer Res., 61, 3250–3255.

  • Hess AR, Seftor EA, Gruman LM, Kinch MS, Seftor REB and Hendrix MJC . (2002). Cancer Res., 43, 36.

  • Holden C and Vogel G . (2002). Science, 296, 2126–2129.

  • Hynes RO . (1992). Curr. Opin. Genet. Dev., 2, 621–624.

  • Kemler R . (1992). Semin. Cell Biol., 3, 149–155.

  • Khan J, Simon R, Bittner M, Chen Y, Leighton SB, Pohida T, Smith PD, Jiang Y, Gooden GC, Trent JM and Meltzer PS . (1998). Cancer Res., 58, 5009–5013.

  • Khan J, Wei JS, Ringner M, Saal LH, Landanyi M, Westermann F, Berthold F, Schwab M, Antonescu CR, Peterson C and Meltzer PS . (2001). Nat. Med., 7, 673–679.

  • Khwaja A, Lehman K, Marte B and Downward J . (1996) J. Biol. Chem., 273, 18793–18801.

  • Kim I, Kim HG, Moon S, Chae SW, So J, Koh KN, Ann BC and Koh GY . (2000). Circul. Res., 86, 952–959.

  • Koshikawa N, Giannelli G, Cirulli V, Miyazaki K and Quaranta V . (2000). J. Cell Biol., 148, 615–624.

  • Kumar R and Fidler IJ . (1998). In Vivo, 12, 27–34.

  • Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP and Dejana E . (1992). J. Cell Biol., 118, 1511–1522.

  • Liotta L and Petricoin E . (2000). Nat. Rev. Genet., 1, 48–56.

  • Malinda KM and Kleinman HK . (1996). Int. J. Biochem. Cell Biol., 28, 957–995.

  • Malinda KM, Motoyoshi N, Melissa C, Delgado M, Kuratomi Y, Yamada Y, Kleinman HK and Ponce ML . (1999). FASEB J., 13, 53–62.

  • Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS and Hendrix MJC . (1999). Am. J. Pathol., 155, 739–752.

  • Maniotis AJ, Chen X, Garcia C, De Christopher PJ, Wu D, Peèr J and Folberg R . (2002). Lab. Invest., 82, 1031–1043.

  • Pandey A, Lazar DF, Saltiel A and Dixit VM . (1994). J. Biol. Chem., 269, 30154–30157.

  • Pasquale EB . (1997). Curr. Opin. Cell Biol., 9, 608–615.

  • Rak J and Kerbel RS . (1996). Cancer Metast. Rev., 15, 231–236.

  • Risau W . (1997). Nature, 386, 671–674.

  • Rosenburg IM, Goke M, Kanai M, Reinecker HC and Podolsky DK . (1997). Am. J. Physiol., 273(Part 1), G824–G832.

  • Seftor EA, Meltzer PS, Kirschmann DA, Pe'er J, Maniotis AJ, Trent JM, Folberg R and Hendrix MJC . (2002). Clin. Exp. Metast., B19, 233–246.

  • Seftor REB, Seftor EA, Koshikawa N, Meltzer PS, Gardner LMG, Bilban M, Stetler-Stevenson WG, Quaranta V and Hendrix MJC . (2001). Cancer Res., 61, 6322–6327.

  • Straume O and Akslen LA . (2001). Am. J. Pathol., 160, 1009–1019.

  • Vogel G . (2002). Science, 295, 1989–1991.

  • Warso MA, Maniotis AJ, Chen X, Majumdar D, Patel MK, Shilkaitis A, Gupta TK and Folberg R . (2001). Clin. Cancer Res., 7, 473–477.

  • Weissman IL . (2000). Cell, 100, 157–168.

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Acknowledgements

We gratefully acknowledge the scientific collaborations with Drs Paul Meltzer and Jeffrey Trent (National Human Genome Research Institute), and Drs Gina Schatteman, Don Sheriff, Dawn Kirschmann, and Ms Lynn Gruman (The University of Iowa). This research was supported by NIH/National Cancer Institute Grants CA80318, CA59702 and CA88043-02S1 (to MJCH), CA83137 (to REBS) and Oncology Research Training Award from The Holden Comprehensive Cancer Center's Institutional National Research Service Award 2 T32 CA79445-03 (to ARH).

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  1. The Holden Comprehensive Cancer Center at The University of Iowa, Roy J and Lucille A Carver College of Medicine, Bowen Science Building, 51 Newton Road, Iowa City, 52242-1109, IA, USA

    Mary J C Hendrix, Elisabeth A Seftor, Angela R Hess & Richard E B Seftor

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  1. Mary J C Hendrix
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  2. Elisabeth A Seftor
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  3. Angela R Hess
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Correspondence to Mary J C Hendrix.

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Hendrix, M., Seftor, E., Hess, A. et al. Molecular plasticity of human melanoma cells. Oncogene 22, 3070–3075 (2003). https://doi.org/10.1038/sj.onc.1206447

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