In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts.
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.
Dimanche-Boitrel
M T
MT
Research Group on Gastrointestinal Cancers, INSERM U-252, Faculty of Medicine, Dijon, France.
Vakaet
L
L
Pujuguet
P
P
Chauffert
B
B
Martin
M S
MS
Hammann
A
A
Van Roy
F
F
Mareel
M
M
Martin
F
F
D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D002645:Chickens; D003110:Colonic Neoplasms / Q000473:pathology*; D005347:Fibroblasts / Q000502:physiology*; D007150:Immunohistochemistry; D009206:Myocardium / Q000473:pathology; D009361:Neoplasm Invasiveness; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D015820:Cadherins