IGF binding protein-6 expression in vascular endothelial cells is induced by hypoxia and plays a negative role in tumor angiogenesis

Chunyang Zhang, Ling Lu, Yun Li, Xianlei Wang, Jianfeng Zhou, Yunzhang Liu, Ping-Ping Fu, Marisa Gallicchio, Leon Ashley Bach, Cunming Duan

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40 Citations (Scopus)

Abstract

Hypoxia stimulates tumor angiogenesis by inducing the expression of angiogenic molecules. The negative regulators of this process, however, are not well understood. Here, we report that hypoxia induced the expression of insulin-like growth factor binding protein-6 (IGFBP-6), a tumor repressor, in human and rodent vascular endothelial cells (VECs) via a hypoxia-inducible factor (HIF)-mediated mechanism. Addition of human IGFBP-6 to cultured human VECs inhibited angiogenesis in vitro. An IGFBP-6 mutant with at least 10,000-fold lower binding affinity for IGFs was an equally potent inhibitor of angiogenesis, suggesting that this action of IGFBP-6 is IGF-independent....
Original languageEnglish
Pages (from-to)2003 - 2012
Number of pages10
JournalInternational Journal of Cancer
Volume130
Issue number9
DOIs
Publication statusPublished - 2012

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