Modulation of matrix metalloproteinase-7 (matrilysin) secretion in coculture of human colon carcinoma cells with fibroblasts from orthotopic and ectopic organs.
Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases that are believed to contribute to the complex process of cancer invasion and metastasis. The secretion level of MMP-7 as assayed by immunoblot analysis was low but distinct in the culture medium of a human colon carcinoma cell line, WIDr, whereas none of the fibroblasts secreted the detectable level of MMP-7. The coculture of WiDr with various human fibroblasts from orthotopic (colon) and ectopic (thyroid, brain, lung, and skin) organs significantly stimulated the secretion of MMP-7 compared with the cultures of individual cells. Reverse transcriptase-polymerase chain reaction analysis and RNA blot analysis suggested that this enhancement occurred at a pretranslational level. The extent of the stimulation was widely varied by the fibroblasts used and was dependent on the cellular ratios and density in the coculture. There may exist a tendency that fibroblasts of orthotopic origin stimulate more extensively than do those of ectopic origin. Moreover, in the coculture of high cell density, normal fibroblasts from the ectopic organs reduced the MMP-7 secretion. The stimulation of MMP-7 secretion may be partially mediated through soluble factor(s); however, direct cell-cell interactions would be required for maximum stimulation. The enhanced MMP-7 secretion was also observed in coculture of colon fibroblasts with other colorectal carcinoma cell lines such as RCM-1 and SW837, which secreted hardly detectable levels of MMP-7 in the individual culture. These results suggest that MMP-7 secretion by colon carcinoma cells is influenced by specific interactions between the carcinoma cells and host fibroblasts.
Kataoka
H
H
Second Department of Pathology, Miyazaki Medical College, Japan.
Meng
J Y
JY
Uchino
H
H
Nabeshima
K
K
Kihira
Y
Y
Matuo
Y
Y
Koono
M
M
D002450:Cell Communication; D003110:Colonic Neoplasms / Q000201:enzymology*; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012636:Secretory Rate / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7