EXPRESSION OF MTS1, A METASTASIS-ASSOCIATED GENE, INCREASES MOTILITY BUT NOT INVASION OF A NONMETASTATIC MOUSE MAMMARY ADENOCARCINOMA CELL-LINE

The mts1 gene codes for a 101 amino acid protein belonging to the S100 subfamily of Ca2+-binding proteins. Mts1 is overexpressed in metastat ic cancers as compared to their nonmetastatic counterparts, and althou gh mts1 is known to be involved in the metastatic phenotype (Davies et al., 1993; Grigorian et al., 1993), the role mts1 plays in this proce ss is not clearly understood. In order to determine what role mts1 pla ys in the process of metastasis, we have transfection studies on nonme tastatic and mouse mammary adenocarcinoma cell lines, CSML0 and CSML10 0, respectively (Senin et al., 1983, 1984). The metastatic variant, CS ML100, expresses high levels of mts1, whereas the nonmetastatic varian t, CSML0, expresses almost no mts1. CSML0 cells transfected with mts1 were assessed in in vitro motility and invasion assays, as web as in v ivo metastasis assays to determine the role of mts1 in these processes , Cell lines expressing mts1 display an altered morphology as, well as increased motility in modified Boyden chemotaxis chambers, However, n o significant increase in in vitro invasion or in in vivo metastasis w as observed. Therefore, the presence of mts1 may be important for meta stasis by increasing motility, but may not be sufficient for invasion in vitro or metastasis in vivo. Very low levels of type IV collagenase activities were observed in CSML0 cells and the transfectants, as opp osed to the highly metastatic CSML100 cells, where high levels of type IV collagenase activities were observed. It is possible that the pres ence of these proteases in addition to mts1 may be responsible for the high metastatic potential of the CSML100 in vivo.