Induction of fibroblast gelatinase B expression by direct contact with cell lines derived from primary tumor but not from metastases.
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 coculture systems to investigate fibroblast interaction with three colon cancer cell lines isolated from a single patient. Cells from primary colorectal carcinoma, but not from corresponding liver or lymph node metastases, induced gelatinase B expression by fibroblasts of different tissue origin. Remarkably, direct cell-cell contact was required for this induction, which occurred at the pretranslational level (as revealed by Northern blot analysis) and was completely blocked by anti-beta1 integrin monoclonal antibody, but only partially blocked by anti-alpha5 or anti-alpha(v). Induction was also inhibited by cytochalasin D, staurosporine, or dexamethasone, suggesting the need, respectively, for an organized actin cytoskeleton, protein kinase C, and AP-1-driven gene transcription. Our data suggest that direct tumor-stromal cell contact is one inductive event involved in matrix metalloproteinase expression by stromal cells.
Segain
J P
JP
Unité Institut National de la Santé et de la Recherche Médicale U 419,Institut de Biologie, Centre Hospitalier Universitaire, Nantes, France.
Harb
J
J
Grégoire
M
M
Meflah
K
K
Menanteau
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology / Q000556:secondary*; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology*; D003238:Connective Tissue / Q000201:enzymology; D003239:Connective Tissue Cells; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D019833:Genistein; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D007529:Isoflavones; D018808:Transcription Factor AP-1; D015638:Cytochalasin D; D003907:Dexamethasone; D019833:Genistein; D011493:Protein Kinase C; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine