Title |
VEGF-B promotes cancer metastasis through a VEGF-A–independent mechanism and serves as a marker of poor prognosis for cancer patients
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, May 2015
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DOI | 10.1073/pnas.1503500112 |
Pubmed ID | |
Authors |
Xiaojuan Yang, Yin Zhang, Kayoko Hosaka, Patrik Andersson, Jian Wang, Fredrik Tholander, Ziquan Cao, Hiromasa Morikawa, Jesper Tegnér, Yunlong Yang, Hideki Iwamoto, Sharon Lim, Yihai Cao |
Abstract |
The biological functions of VEGF-B in cancer progression remain poorly understood. Here, we report that VEGF-B promotes cancer metastasis through the remodeling of tumor microvasculature. Knockdown of VEGF-B in tumors resulted in increased perivascular cell coverage and impaired pulmonary metastasis of human melanomas. In contrast, the gain of VEGF-B function in tumors led to pseudonormalized tumor vasculatures that were highly leaky and poorly perfused. Tumors expressing high levels of VEGF-B were more metastatic, although primary tumor growth was largely impaired. Similarly, VEGF-B in a VEGF-A-null tumor resulted in attenuated primary tumor growth but substantial pulmonary metastases. VEGF-B also led to highly metastatic phenotypes in Vegfr1 tk(-/-) mice and mice treated with anti-VEGF-A. These data indicate that VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism. High expression levels of VEGF-B in two large-cohort studies of human patients with lung squamous cell carcinoma and melanoma correlated with poor survival. Taken together, our findings demonstrate that VEGF-B is a vascular remodeling factor promoting cancer metastasis and that targeting VEGF-B may be an important therapeutic approach for cancer metastasis. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Peru | 1 | 50% |
Japan | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Sweden | 2 | 2% |
United States | 1 | <1% |
France | 1 | <1% |
Switzerland | 1 | <1% |
Unknown | 117 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 20 | 16% |
Student > Bachelor | 18 | 15% |
Researcher | 13 | 11% |
Other | 8 | 7% |
Student > Master | 8 | 7% |
Other | 27 | 22% |
Unknown | 28 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 25 | 20% |
Medicine and Dentistry | 23 | 19% |
Agricultural and Biological Sciences | 16 | 13% |
Immunology and Microbiology | 6 | 5% |
Chemistry | 4 | 3% |
Other | 19 | 16% |
Unknown | 29 | 24% |