PUBLICATION
VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients
- Authors
- Yang, X., Zhang, Y., Hosaka, K., Andersson, P., Wang, J., Tholander, F., Cao, Z., Morikawa, H., Tegnér, J., Yang, Y., Iwamoto, H., Lim, S., Cao, Y.
- ID
- ZDB-PUB-170214-182
- Date
- 2015
- Source
- Proceedings of the National Academy of Sciences of the United States of America 112: E2900-9 (Journal)
- Registered Authors
- Wang, Jian
- Keywords
- VEGF-A, VEGF-B, VEGFR1, angiogenesis, metastasis
- MeSH Terms
-
- Animals
- Biomarkers, Tumor/metabolism*
- Blotting, Western
- Cell Hypoxia
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- Fluorescent Antibody Technique
- Immunohistochemistry
- Injections, Subcutaneous
- Kaplan-Meier Estimate
- Mice
- Microvessels/drug effects*
- Neoplasm Metastasis/physiopathology*
- Neoplasms/blood supply*
- Polymerase Chain Reaction
- Vascular Endothelial Growth Factor B/administration & dosage
- Vascular Endothelial Growth Factor B/metabolism*
- Vascular Endothelial Growth Factor B/pharmacology*
- Zebrafish
- PubMed
- 25991856 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Yang, X., Zhang, Y., Hosaka, K., Andersson, P., Wang, J., Tholander, F., Cao, Z., Morikawa, H., Tegnér, J., Yang, Y., Iwamoto, H., Lim, S., Cao, Y. (2015) VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients. Proceedings of the National Academy of Sciences of the United States of America. 112:E2900-9.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping