ACQUISITION OF INVASIVE PHENOTYPE IN GALLBLADDER CANCER-CELLS VIA MUTUAL INTERACTION OF STROMAL FIBROBLASTS AND CANCER-CELLS AS MEDIATED BYHEPATOCYTE GROWTH-FACTOR
K. Matsumoto et al., ACQUISITION OF INVASIVE PHENOTYPE IN GALLBLADDER CANCER-CELLS VIA MUTUAL INTERACTION OF STROMAL FIBROBLASTS AND CANCER-CELLS AS MEDIATED BYHEPATOCYTE GROWTH-FACTOR, Japanese journal of cancer research, 87(7), 1996, pp. 702-710
Growth and motility of carcinoma cells are regulated through their int
eractions with host stromal cells, i.e., tumor-stromal interactions. H
epatocyte growth factor (HGF), a ligand for c-Met tyrosine kinase, is
a stromal-derived regulator of growth, motility, and morphogenesis. HG
F stimulated proliferation and motility of GB-d1 gallbladder carcinoma
cells from a patient with gallbladder cancer. HGF induced in vitro in
vasion of GB-d1 cells into a collagen gel matrix, and this potent, inv
asive effect was not seen with epidermal growth factor, transforming g
rowth factor-beta 1, basic fibroblast growth factor, or platelet-deriv
ed growth factor. Although GB-d1 did not produce HGF, the cells did pr
oduce 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 m
atrix 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 w
as inhibited by antibodies against HGF and partially inhibited by anti
bodies against IL-1 beta. Thus, GB-d1 cell-derived IL-1 beta stimulate
s HGF production in stromal fibroblasts and HGF up-regulated in the fi
broblasts induces invasion of GB-d1 cells, The looped interaction of c
arcinoma cells and stromal fibroblasts mediated by HGF and a HGF-induc
er such as IL-1 beta may be one mechanism which would explain the acqu
isition of malignant phenotype through tumor-stromal interactions.