The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR.

Abstract

New therapeutic approach is required for pancreatic cancer, one of the most intractable malignancies. The role of angiogenesis in the tumor growth of a Syrian hamster pancreatic cancer cell line HPD-NR, which closely resembles its human counterpart, was investigated. Angiogenic activity was measured as stimulation of growth of human umbilical vein endothelial cells (HUVEC), and angiogenic factors produced by HPD-NR cells were identified by reverse-transcription polymerase chain reaction and Northern blot analysis. Then in vitro and in vivo antitumor effects of a potent angiogenesis inhibitor, O-(chloroacetylcarbamoyl)fumagillol (AGM-1470), were examined. The conditioned medium of HPD-NR cells stimulated the growth of HUVEC, and four hamster angiogenic factors were detected with an overexpression of transforming growth factor alpha and vascular endothelial growth factor messenger RNAs. AGM-1470 specifically inhibited the growth of HUVEC and that of HPD-NR tumors in vivo with decreased vascularity of the tumors but not the growth of HPD-NR cells in vitro. The results suggest that angiogenesis plays an important role in tumor growth of HPD-NR cells and can be a new target of medical therapy for pancreatic cancer.