IN-VIVO AND IN-VITRO INVASIVENESS OF A RAT COLON-CANCER CELL-LINE MAINTAINING E-CADHERIN EXPRESSION - AN ENHANCING ROLE OF TUMOR-ASSOCIATEDMYOFIBROBLASTS

In various cell systems, an inverse relationship was found between exp ression of E-cadherin, a molecule involved in the Ca2+-dependent homop hylic 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 c arcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assay s. PROb cells were found to be non-invasive in 3 different assays in v itro. However, tumors resulting from a s.c. injection of PROb cells in to syngeneic BD-IX rats were invasive, although PROb eels maintained E -cadherin expression in the tumors. Cells from a freshly dissociated P ROb tumor showed, not only PROb cells but also tumor-associated myofib roblasts 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 t umor-infiltrating myofibroblasts were able to confer upon PROb cells i nvasiveness through Matrigel-coated filter or into chick-heart fragmen ts. PROb cells maintained their capacity to express E-cadherin after m yofibroblast-enhanced Matrigel invasion, Tumor-associated myofibroblas ts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cel ls 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 differe nt in vitro assays. (C) 1994 Wiley-Liss, Inc.