Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)418-431
Number of pages14
JournalJournal of Clinical Investigation
Volume123
Issue number1
DOIs
StatePublished - Jan 2 2013

Fingerprint

Neoplasms
Blood Vessels
Genetic Models
Myeloid Cells
Glioblastoma
Growth
Transcription Factors
Neoplasm Metastasis
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yang, H., Lee, S., Lee, S., Kim, K., Yang, Y., Kim, J. H., ... Kim, I. (2013). Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice. Journal of Clinical Investigation, 123(1), 418-431. https://doi.org/10.1172/JCI64547

Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice. / Yang, Hanseul; Lee, Sungsu; Lee, Seungjoo; Kim, Kangsan; Yang, Yeseul; Kim, Jeong Hoon; Adams, Ralf H.; Wells, James M.; Morrison, Sean J.; Koh, Gou Young; Kim, Injune.

In: Journal of Clinical Investigation, Vol. 123, No. 1, 02.01.2013, p. 418-431.

Research output: Contribution to journalArticle

Yang, H, Lee, S, Lee, S, Kim, K, Yang, Y, Kim, JH, Adams, RH, Wells, JM, Morrison, SJ, Koh, GY & Kim, I 2013, 'Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice', Journal of Clinical Investigation, vol. 123, no. 1, pp. 418-431. https://doi.org/10.1172/JCI64547
Yang, Hanseul ; Lee, Sungsu ; Lee, Seungjoo ; Kim, Kangsan ; Yang, Yeseul ; Kim, Jeong Hoon ; Adams, Ralf H. ; Wells, James M. ; Morrison, Sean J. ; Koh, Gou Young ; Kim, Injune. / Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 1. pp. 418-431.
@article{20b967c95d7f476391e6993d4cff7b87,
title = "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.",
author = "Hanseul Yang and Sungsu Lee and Seungjoo Lee and Kangsan Kim and Yeseul Yang and Kim, {Jeong Hoon} and Adams, {Ralf H.} and Wells, {James M.} and Morrison, {Sean J.} and Koh, {Gou Young} and Injune Kim",
year = "2013",
month = "1",
day = "2",
doi = "10.1172/JCI64547",
language = "English (US)",
volume = "123",
pages = "418--431",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice

AU - Yang, Hanseul

AU - Lee, Sungsu

AU - Lee, Seungjoo

AU - Kim, Kangsan

AU - Yang, Yeseul

AU - Kim, Jeong Hoon

AU - Adams, Ralf H.

AU - Wells, James M.

AU - Morrison, Sean J.

AU - Koh, Gou Young

AU - Kim, Injune

PY - 2013/1/2

Y1 - 2013/1/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84873843115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873843115&partnerID=8YFLogxK

U2 - 10.1172/JCI64547

DO - 10.1172/JCI64547

M3 - Article

C2 - 23241958

AN - SCOPUS:84873843115

VL - 123

SP - 418

EP - 431

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -