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 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.

Cloning and functional characterization of a new phosphatidyl-inositol anchored molecule of a metastasizing rat pancreatic tumor

“…that the uPAR and the C4.4A on BSp73ASML cells are occupied by uPA and/or the not yet de®ned proper ligand of C4.4A. Finally, as also described for the uPAR, it could well be that C4.4A transfected BSp73AS cells can recruit in vivo uPA and/ or related molecules from host cells (Dimanche-Boitrel et al, 1994). Taking into account this possibility it becomes comprehensible that C4.4A transfected cells degrade in vivo e ciently surrounding tissue, but hardly a layer of matrigel in vitro.…”

Role of tissue stroma in cancer cell invasion

“…Stromal cells of interest are myofibroblasts, as suggested by our previous experiments [18]. During epithelial carcinogenesis, the efferent signalling changes (dotted thick arrow) and this causes cancer-associated changes in the stroma.…”

miR-186 Regulates Glycolysis through Glut1 During the Formation of Cancer-associated Fibroblasts

“…Through specific communication with cancer cells, CAFs can directly promote tumor initiation, progression and metastasis (Dimanche-Boitrel et al, 1994;Olaso et al, 1997;Olumi et al, 1999;Bhowmick et al, 2004;Kuperwasser et al, 2004;Grum-Schwensen et al, 2005;Orimo et al, 2005). CAFs secrete growth factors and ECM-degrading proteases to promote tumor growth and invasiveness.…”