IN-VIVO AND IN-VITRO INVASIVENESS OF A RAT COLON-CANCER CELL-LINE MAINTAINING E-CADHERIN EXPRESSION - AN ENHANCING ROLE OF TUMOR-ASSOCIATEDMYOFIBROBLASTS
Mt. Dimancheboitrel et al., IN-VIVO AND IN-VITRO INVASIVENESS OF A RAT COLON-CANCER CELL-LINE MAINTAINING E-CADHERIN EXPRESSION - AN ENHANCING ROLE OF TUMOR-ASSOCIATEDMYOFIBROBLASTS, International journal of cancer, 56(4), 1994, pp. 512-521
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.