Jp. Segain et al., INDUCTION OF FIBROBLAST GELATINASE-B EXPRESSION BY DIRECT-CONTACT WITH CELL-LINES DERIVED FROM PRIMARY TUMOR BUT NOT FROM METASTASES, Cancer research, 56(23), 1996, pp. 5506-5512
During cancer progression, tumor cells interact with stromal cells. As
a consequence, matrix metalloproteinases are produced that contribute
to the degradation of the extracellular matrix. This study used cocul
ture systems to investigate fibroblast interaction with three colon ca
ncer cell lines isolated from a single patient. Cells from primary col
orectal carcinoma, but not from corresponding liver or lymph node meta
stases, induced gelatinase B expression by fibroblasts of different ti
ssue origin. Remarkably, direct cell-cell contact was required for thi
s induction, which occurred at the pretranslational level (as revealed
by Northern blot analysis) and was completely blocked by anti-beta 1
integrin. monoclonal antibody, but only partially blocked by anti-alph
a 5 or anti-alpha v. Induction was also inhibited by cytochalasin D, s
taurosporine, or dexamethasone, suggesting the need, respectively, for
an organized actin cytoskeleton, protein kinase C, and AP-1-driven ge
ne transcription. Our data suggest that direct tumor-stromal cell cont
act is one inductive event involved in matrix metalloproteinase expres
sion by stromal cells.