Transforming growth factor-beta and hepatocyte growth factor produced by gastric fibroblasts stimulate the invasiveness of scirrhous gastric cancer cells.
Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts. In the present study, we examined the effect of gastric fibroblasts on the invasiveness of a scirrhous gastric cancer cell line, OCUM-2D, using an invasion assay. Gastric fibroblast-derived conditioned medium (CM) significantly stimulated the invasiveness of OCUM-2D cells, as did transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF). The stimulating activity of gastric fibroblast-derived CM was inhibited significantly by anti-TGF-beta neutralizing antibody or anti-HGF neutralizing antibody. TGF-beta and HGF were detected in the gastric fibroblast-derived CM, and TGF-beta receptor and C-met (HGF receptor) were expressed on OCUM-2D cells. Thus, TGF-beta and HGF produced by gastric fibroblasts appear to affect the invasiveness of scirrhous gastric cancer cells. TGF-beta was also detected in the conditioned medium derived from OCUM-2D cells, though HGF was not. TGF-beta appears to affect the invasiveness of OCUM-2D cells in both paracrine and autocrine fashions.
Inoue
T
T
First Department of Surgery, Osaka City University Medical School.
Chung
Y S
YS
Yashiro
M
M
Nishimura
S
S
Hasuma
T
T
Otani
S
S
Sowa
M
M
D002293:Adenocarcinoma, Scirrhous / Q000556:secondary*; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016207:Cytokines; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor