Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts

Abstract

Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of welldifferentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10 000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-a (TGF-a), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor ,B1 (TGF-,B1) may play an important role in the progression of scirrhous gastric cancer cells.

Cancer–Stromal Interactions in Scirrhous Gastric Carcinoma

“…The interaction between gastric cancer cells and organspecific fibroblasts is evident in vivo [8] and in vitro [6]. Co-inoculation of scirrhous gastric cancer cells with gastric fibroblasts into nude mice specifically increases tumorigenicity, in comparison to that of gastric cancer cells alone (Fig.…”

“…Scirrhous carcinomas account for about 10% of all gastric carcinomas, and carry a worse prognosis than other types of gastric carcinoma, reflecting their rapid proliferation of cancer cells [3][4][5]. The common features of scirrhous gastric cancer include rapidly progressive invasion, and a high frequency of metastasis to the peritoneum [6]. Scirrhous gastric cancer cells proliferate with fibrosis when the cancer cells invade into the submucosa containing abundant stromal cells.…”

Interferon-γ suppresses transforming growth factor-β-induced invasion of gastric carcinoma cells through cross-talk of Smad pathway in a three-dimensional culture model

“…Fibroblasts, vascular endothelial cells, macrophages, and other cells organize the tumor microenvironment. Of the various stromal cells, fibroblasts play an essential role in producing the growth factors and the extracellular matrix, which may promote the proliferation and invasion of carcinoma cells (Yashiro et al, 1996;Kunz-Schughart et al, 2001). The extracellular matrix is another important component forming the tumor microenvironment, providing the structure, generating biological signals, storing factors that generate biological signals, and exerting mechanical influence on both the carcinoma and stromal cells (Matrisian et al, 2001).…”

“…Various growth factors that effect carcinoma invasion are produced by both the carcinoma and stromal cells in carcinoma tissue (Ura et al, 1991;Yashiro et al, 1996;Kunz-Schughart et al, 2001). It is generally thought that the transforming growth factor-b (TGF-b) plays an important role in the aggression of gastric carcinoma, especially in promoting the highly invasive nature of carcinoma cells (Nakamura et al, 1998;Ellenrieder et al, 2001;Pasche, 2001).…”

Effects of VEGFR-3 phosphorylation inhibitor on lymph node metastasis in an orthotopic diffuse-type gastric carcinoma model

“…The characteristic clinical features of diffuse-type gastric carcinoma (DGC), a diffusely infiltrating type of gastric carcinoma also known as scirrhous gastric carcinoma, include a high frequency of metastasis to the LNs (Hippo et al, 2001;Nakazawa et al, 2003) and to the peritoneum (Yashiro et al, 1996;Takemura et al, 2004;Tendo et al, 2005). Although we currently reported the effects of Ki23057 on the peritoneal dissemination of DGC with an amplification of the activated FGF-R2 (K-samII) gene (Shimizu et al, 2004;Nakamura et al, 2006), no candidate agent as VEGFR-3 phosphorylation inhibitor has yet been proposed for the molecular target therapy of LN metastasis.…”