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Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro

Oncogene volume 20, pages 270–275 (2001)Cite this article

Abstract

Resistance to apoptosis and ability to promote angiogenesis are integral features of the metastatic phenotype. Human gene CC3 is a metastasis suppressor for variant small cell lung carcinoma and a mouse melanoma in vivo. We have shown previously that metastasis-suppressing function of CC3 might be due at least in part to the ability of CC3 protein to predispose tumor cells to apoptosis. Here we demonstrate that CC3 has a previously unidentified effect on the ability of tumor cells to induce angiogenesis in vitro. Expression of CC3 in three different tumor cell lines significantly diminished their angiogenic character as manifested in the in vitro proliferation and migration assays with endothelial cells of both macro- and microvascular origin. Expression of CC3 induced changes in RNA levels of several angiogenic modulators consistent with the overall reduction in angiogenic properties. These results indicate that expression of CC3 has a dual effect on phenotype of tumor cells ultimately inhibiting their metastatic potential.

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References

  • Addison CL, Arenberg DA, Morris SB, Xue YY, Burdick MD, Mulligan MS, Iannettoni MD and Strieter RM. . 2000 Hum. Gene. Ther. 11: 247–261.

  • Baker ME. . 1999 Curr Biol. 9: R471.

  • Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W and Bouck NP. . 1999 Science 285: 245–248.

  • Dearing MP, Steinberg SM, Phelps R, Anderson MJ, Mulshine JL, Ihde DC and Johnson BE. . 1990 J. Clin. Oncol. 8: 1042–1049.

  • Gentilini G, Kirschbaum NE, Augustine JA, Aster RH and Visentin GP. . 1999 Blood 93: 25–33.

  • Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA and Bouck NP. . 1990 Proc. Natl. Acad. Sci. USA 87: 6624–6628.

  • Hanahan D and Folkman J. . 1996 Cell 86: 353–364.

  • Holmgren L, O'Reilly MS and Folkman J. . 1995 Nat. Med. 1: 149–153.

  • Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U and Risau W. . 1998 Curr. Biol. 8: 529–532.

  • Kupprion C, Motamed K and Sage EH. . 1998 J. Biol. Chem. 273: 29635–29640.

  • Liu Y, Thor A, Shtivelman E, Cao Y, Guanghuan T, Heath TD and Debs RJ. . 1999 J. Biol. Chem. 274: 13338–13344.

  • Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN and Yancopoulos GD. . 1997 Science 277: 55–60.

  • Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y and Tokino T. . 1997 Oncogene 15: 2145–2150.

  • O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR and Folkman J. . 1997 Cell 88: 277–285.

  • O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH and Folkman J. . 1994 Cell 79: 315–328.

  • Shtivelman E. . 1997 Oncogene 14: 2167–2173.

  • Shtivelman E and Namikawa R. . 1995 Proc. Natl. Acad. Sci. USA 92: 4661–4665.

  • Strieter RM, Kunkel SL, Arenberg DA, Burdick MD and Polverini PJ. . 1995 Biochem. Biophys. Res. Commun. 210: 51–57.

  • Vazquez F, Hastings G, Ortega MA, Lane TF, Oikemus S, Lombardo M and Iruela-Arispe ML. . 1999 J. Biol. Chem. 274: 23349–23357.

  • Whitman S, Wang X, Shalaby R and Shtivelman E. . 2000 Mol. Cell. Biol. 20: 583–593.

  • Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD and Isner JM. . 1998 J. Biol. Chem. 273: 18514–18521.

  • Xiao H, Palhan V, Yang Y and Roeder RG. . 2000 EMBO J. 19: 956–963.

  • Xiao H, Tao Y, Greenblatt J and Roeder RG. . 1998 Proc. Natl. Acad. Sci. USA 95: 2146–2151.

  • Zhai Y, Ni J, Jiang GW, Lu J, Xing L, Lincoln C, Carter KC, Janat F, Kozak D, Xu S, Rojas L, Aggarwal BB, Ruben S, Li LY, Gentz R and Yu GL. . 1999 FASEB J. 13: 181–189.

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Acknowledgements

We are grateful to Dr Eleni Venetsanakos for the gift of immortalized human fibroblasts, to Dr Nishimori for the BAI1 cDNA, to Josh Sussman for statistical analysis and to Drs Karen Smith-McCune and Robert J. Debs for the critical reading of the manuscript. This work was supported by funds from NIH grant RO1 CA71422 and an award from the Stewart Foundation, UCSF.

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  1. Cancer Research Institute, University of California San Francisco, 2340 Sutter Street, San Francisco, 94143-0128, California, CA, USA

    Roisin NicAmhlaoibh & Emma Shtivelman

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  1. Roisin NicAmhlaoibh
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  2. Emma Shtivelman
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NicAmhlaoibh, R., Shtivelman, E. Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro. Oncogene 20, 270–275 (2001). https://doi.org/10.1038/sj.onc.1204075

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