header logo image header logo text
Downloads Login
General Information
ZFIN ID: ZDB-PUB-170214-182
VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients
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.
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
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.