In vitro invasiveness of human epithelioid‐sarcoma cell lines: Association with cell motility and inverse correlation with the expression of tissue inhibitor of metalloproteinases

Epithelioid sarcoma (ES) is a very aggressive soft-tissue tumor in vivo, but no experimental data on its invasive and metastatic behavior have been reported. In the present study, 3 different clonal sub-populations (GRU-1A, GRU-1B and GRU-1C), derived from the same human ES cell line, GRU-1, were investigated for in vitro invasiveness in relation to migration, adhesion and the expression of different invasion- and metastasis-related genes. Tumor spheroids of GRU-1A were markedly more invasive in the chick-heart invasion assay (CHIA) than spheroids of GRU-1B and GRU-1C. These results were paralleled by a significantly higher cell motility of GRU-1A than GRU-1B and GRU-1C (p < 0.05) on distinct substrates, suggesting that the observed differences in invasion result at least in part from differences in motility. When invasion was assayed with suspended tumor cells in the Matrigel assay, differences between the 3 cell lines were much more pronounced than in the CHIA, where cell-cell contacts are established. These results indicate that interclonal differences in ES invasion result mainly from differences in motility, but also partly depend on differences in cell-cell adhesion. On the molecular level, low invasive potential was associated with over-expression of distinct tissue inhibitor of metalloproteinases (TIMPs) relative to matrix metalloproteinase-2 and -9. However, no association was found between invasion and the expression of CD44 splicing variants or nm23 isoforms. Our results suggest that differences in invasion between GRU-1A, GRU-1B and GRU-1C are caused mainly by interclonal differences in migration, and might result from differences in the expression of distinct TIMPs. Int. J. Cancer 80:406–412, 1999. © 1999 Wiley-Liss, Inc.