title: Acquisition of invasive phenotype in gallbladder cancer cells via mutual interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor.
abstract: Growth and motility of carcinoma cells are regulated through their interactions with host stromal cells, i.e., tumor-stromal interactions. Hepatocyte growth factor (HGF), a ligand for c-Met tyrosine kinase, is a stromal-derived regulator of growth, motility, and morphogenesis. HGF stimulated proliferation and motility of GB-d1 gallbladder carcinoma cells from a patient with gallbladder cancer. HGF induced in vitro invasion of GB-d1 cells into a collagen gel matrix, and this potent, invasive effect was not seen with epidermal growth factor, transforming growth factor-beta 1, basic fibroblast growth factor, or platelet-derived growth factor. Although GB-d1 did not produce HGF, the cells did produce a factor which enhances HGF production in human skin fibroblasts, and this factor proved to be interleukin-1 beta (IL-1 beta). When GB-d1 cells were co-cultured with fibroblasts such that a collagen gel matrix was layered between the GB-d1 cells and fibroblasts, GB-d1 cells invaded the gel, but invasion of the cells in the co-culture system was inhibited by antibodies against HGF and partially inhibited by antibodies against IL-1 beta. Thus, GB-d1 cell-derived IL-1 beta stimulates HGF production in stromal fibroblasts and HGF up-regulated in the fibroblasts induces invasion of GB-d1 cells. The looped interaction of carcinoma cells and stromal fibroblasts mediated by HGF and a HGF-inducer such as IL-1 beta may be one mechanism which would explain the acquisition of malignant phenotype through tumor-stromal interactions.
authors.affiliation: Division of Biochemistry, Osaka University Medical School.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Date
authors.forename: H
authors.initials: H
authors.lastname: Shimura
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D002450:Cell Communication / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology; D005706:Gallbladder Neoplasms / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D010641:Phenotype; D017154:Stromal Cells / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D017228:Hepatocyte Growth Factor