A new level of regulation


Angiogenesis, or the formation of new blood vessels, is important for tumor growth. While many regulatory growth factors have been identified, little is known about the genetic regulation that promotes tumor angiogenesis. Yang et al. examined the expression of SOX17, a protein that regulates gene expression in blood vessel-forming endothelial cells during development. Using a mouse model of tumor angiogenesis, Yang and colleagues found that increased levels of SOX17 promoted tumor angiogenesis, while loss of SOX17 reduced angiogenesis and tumor growth. These results suggest that SOX17 is a potential therapeutic target to decrease angiogenesis and tumor growth.  

Published December 17, 2012, by Jillian Hurst

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Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice
Hanseul Yang, … , Gou Young Koh, Injune Kim
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Published December 17, 2012
Citation Information: J Clin Invest. 2013;123(1):418-431. https://doi.org/10.1172/JCI64547.
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Research Article Oncology

Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice

Abstract

Little is known about the transcriptional regulation of tumor angiogenesis, and tumor ECs (tECs) remain poorly characterized. Here, we studied the expression pattern of the transcription factor Sox17 in the vasculature of murine and human tumors and investigated the function of Sox17 during tumor angiogenesis using Sox17 genetic mouse models. Sox17 was specifically expressed in tECs in a heterogeneous pattern; in particular, strong Sox17 expression distinguished tECs with high VEGFR2 expression. Whereas overexpression of Sox17 in tECs promoted tumor angiogenesis and vascular abnormalities, Sox17 deletion in tECs reduced tumor angiogenesis and normalized tumor vessels, inhibiting tumor growth. Tumor vessel normalization by Sox17 deletion was long lasting, improved anticancer drug delivery into tumors, and inhibited tumor metastasis. Sox17 promoted endothelial sprouting behavior and upregulated VEGFR2 expression in a cell-intrinsic manner. Moreover, Sox17 increased the percentage of tumor-associated CD11b+Gr-1+ myeloid cells within tumors. The vascular effects of Sox17 persisted throughout tumor growth. Interestingly, Sox17 expression specific to tECs was also observed in highly vascularized human glioblastoma samples. Our findings establish Sox17 as a key regulator of tumor angiogenesis and tumor progression.

Authors

Hanseul Yang, Sungsu Lee, Seungjoo Lee, Kangsan Kim, Yeseul Yang, Jeong Hoon Kim, Ralf H. Adams, James M. Wells, Sean J. Morrison, Gou Young Koh, Injune Kim

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