In vivo and in vitro invasiveness of a rat colon‐cancer cell line maintaining E‐cadherin expression: An enhancing role of tumor‐associated myofibroblasts

Abstract

In various cell systems, an inverse relationship was found between expression of E‐cadherin, a molecule involved in the Ca²⁺‐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 myofibrobfasts 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.