Enforced Expression of METCAM Enhances the in vivo Tumorigenesis and in vitro Motility and Invasiveness of a Human Ovarian Cancer Cell Line, BG-1.
¹Eugene Lee Son and Guang-Jer Wu
¹Department of Microbiology & Immunology and The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA

Abstract

Background. Epithelial ovarian cancer is the leading cause of death from gynecological cancers in the United States. Because of the inability to detect the disease at an early stage and the lack of therapies to treat the advanced stages, there is a need for new therapeutic targets through a better knowledge of the mechanisms of the carcinoma and metastasis. The invasive properties of ovarian carcinoma cells are determined by different signaling pathways, which can become new molecular targets for new therapies. METCAM is a cell adhesion molecule that can affect cell motility, cell-cell interactions, and cell-extracellular matrix interactions via many signaling pathways. Recent findings have shown that METCAM is overly expressed in ovarian cancer tissues and in metastatic lesions in the ovary (Wu et al., 2006). Metastasis of ovarian cancer is different from other typical metastatic mechanisms because it can start metastasis before a well-developed tumor has formed. This may suggest that METCAM can play a role in initiating the metastasis of ovarian cancer cells. To test this hypothesis, we further investigated the possible role of METCAM in the progression of human ovarian cancer.

Methods and Materials

The ovarian cancer cell line, BG-1, was transfected with the wild type (WT) and various truncated forms of the METCAM cDNA, which were in a mammalian cell expressible vector, pcDNA3.1+. G418R-BG-1 clones with differing levels of METCAM expression determined by Western blot analysis were selected for testing for in vitro motility and invasiveness as well as in vivo tumorigenesis. For the test of in vivo tumorigenicity, BG-1 clones/cells were subcutaneously co-injected with Matrigel in athymic nude mice.

Results

Higher METCAM expression significantly increased the in vitro motility and invasiveness of BG-1 cells. However, the enforced expression of either the ectodomain or the cytoplasmic domain did not significantly affect cell motility and invasiveness. Higher METCAM expression also directly increased the in vivo tumor-take, but somewhat increased the in vivo tumor proliferation rate of the BG-1 cells. Enforced expression of either the ectodomain or the cytoplasmic domain significantly increased the tumor-take, but only the cytoplasmic domain significantly increased the tumor proliferation.

Conclusions and Future Studies

Taken together, we conclude that METCAM is proven to be an important determinant in enhancing the tumorigenesis and the metastasis of BG-1 ovarian cancer cells in a xenograft mouse model. The joined functions of both the ectodomain and cytoplasmic domain contribute to these processes.