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. 2001 Aug;85(4):612–617. doi: 10.1054/bjoc.2001.1941

Enhanced VEGF production and decreased immunogenicity induced by TGF-β 1 promote liver metastasis of pancreatic cancer

H Teraoka 1, T Sawada 1, T Nishihara 1, M Yashiro 1, M Ohira 1, T Ishikawa 1, H Nishino 1, K Hirakawa 1
PMCID: PMC2364097  PMID: 11506504

Abstract

TGF-βs are multifunctional polypeptides that regulate cell growth and differentiation, extracellular matrix deposition, cellular adhesion properties, angiogenesis and immune functions. In this study, we investigated the effect of TGF-β1 on liver metastasis and its mechanism by using human pancreatic cancer cell lines Panc-1, Capan-2, and SW1990. Capan-2 and SW1990 cells demonstrated enhanced liver metastatic potential by in vivo splenic injection with TGF-β1. Consequently, we examined the role of TGF-β1 on in vitro angiogenesis and received cytotoxicity by peripheral blood mononuclear leukocytes (PBMLs). While TGF-β1 slightly decreased cell proliferation, it also upregulated VEGF production in all cancer cells examined. The binding of PBMLs to cancer cells and cancer cell cytotoxicity during co-culture with PBMLs were remarkably decreased by treatment with TGF-β1. Panc-1 cells revealed no liver metastasis despite their high immunogenetic and angiogenetic abilities, which was attributed to a lack of expression of the cell surface carbohydrates that induce attachment to endothelial cells. We concluded that the presence of TGF-β1 in the microenvironment of tumour site might play an important role in enhancing liver metastasis of pancreatic cancer by modulating the capacity of angiogenesis and immunogenicity. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: TGF-β 1, liver metastasis, pancreatic cancer, VEGF

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Selected References

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