Abstract 481: METCAM promotes in vitro motility, invasiveness and colony formation, and in vivo tumorigenesis of human breast cancer cells

Abstract

Abstract METCAM (alternative names are MUC18, CD146, S-endo 1, MelCAM, and MCAM) is an integral membrane CAM in the Ig-like gene super-family because it has an immunoglobulin-like extra-cellular domain and a cytoplasmic domain, which contains five consensus sequences potentially to be phosphorylated by PKA, PKC, and CK2. METCAM, as predicted from the protein structure, is capable of performing typical functions of CAMs, such as cell-cell interaction, cell-extracellular matrix interaction, and cross-talk with many signaling pathways. Thus altered expression of METCAM should change cell motility and cellular invasiveness, alters angiogenesis, and affects cellular survival and growth. Consistent with this notion, aberrant expression of METCAM positively associates with the malignant progression of melanoma and prostate cancer. However, the role of METCAM in the progression of human breast cancer cells has been controversial. Two groups suggest that METCAM plays a tumor suppressor role in the development of breast cancer. Two other groups suggest the opposite role. To resolve this controversy, we reinvestigate the role of METCAM in the progression of breast cancer cells. We transfected the METCAM cDNA gene into two breast cancer cell lines, MCF-7 and SKBR3, and isolated G418-resistant clones, which expressed high levels of the protein, for testing the effect of enforced expression of the protein on their in vitro and in vivo cellular behaviors. We have found that METCAM is not expressed or very weakly expressed in five luminal breast cancer cell lines, MCF-7, T47D, BT-10, BT474, and SK-BR-3, but moderately expressed in two basal cell-like breast cancer cell lines, MDA-MB231 and 468. Enforced expression of METCAM in two breast cancer cell lines, MCF-7 and SKBR3, increased their in vitro motility and invasiveness and in vitro anchorage-independent colony growth, and promoted disorganized growth in 3D basement membrane culture. Enforce expression of METCAM also increased the in vitro motility and invasiveness of MDA-MB231 and MDA-MB-468 cells. Furthermore, the growth of MDA-MB231 and MDA-MB-468 in the 3D embedded basement membrane culture is inhibited by the anti-huMETCAM antibodies. Furthermore, enforced expression of METCAM dramatically promoted the tumor formation of SK-BR-3 cells in nude mice, but slightly promoted the tumor formation of MCF7 cells in SCID mice via orthotopic injection into mammary fat pads. Taken together, we concluded that over-expression of METCAM in breast cancer cell lines appeared to promote the tumorigenesis of breast cancer cells, suggesting its positive association with the progression of breast cancer cells, similar to melanoma and prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 481.