From an established cell culture line obtained from a chemically-induced rat colon carcinoma, two sublines have been selected and isolated according to their susceptibility to trypsin-mediated detachment from plastic surfaces. Subline TR, the most resistant to the detaching effect of trypsin, gave progressive tumors in most of the syngeneic rats in which it was inoculated. Subline TS, which was easily detached by trypsin, also gave tumors in the syngeneic rats, but all these tumors disappeared within 3 or 4 weeks. Both sublines gave progressive tumors when injected into nude mice. This suggests that the parent cell line is heterogeneous and contains cell variants differing in their susceptibility to trypsin-mediated detachment from substrate and their sensitivity to host factors leading to acceptance or rejection of the inoculated tumor cells.

No abstract

In various cell systems, an inverse relationship was found between expression of E-cadherin, a molecule involved in the Ca(2+)-dependent homophylic cell-to-cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro. DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assays. PROb cells were found to be non-invasive in 3 different assays in vitro. However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD-IX rats were invasive, although PROb cells maintained E-cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor-associated myofibroblasts and were able to cross a Matrigel-coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor-infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel-coated filter or into chick-heart fragments. PROb cells maintained their capacity to express E-cadherin after myofibroblast-enhanced Matrigel invasion. Tumor-associated myofibroblasts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E-cadherin expression prevents tumor-cell invasiveness in different in vitro assays.