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.

Biography:

Patrik Andersson received his B.Sc. at the age of 21 within biomedical sciences and is now pursuing his Ph.D. studies on the topic of tumor lymphand heme angiogenesis in promoting metastasis. He is receiving his training at the Karolinska Institutet, Sweden under the supervision of Professor Yihai Cao. He was invited as a speaker at the prestigious Gordon Conference in angiogenesis (2013) and at the International Cancer and Prevention methods conference (2015). He has obtained several research and travel grants, and has co-authored ten peer-reviewed articles either published or under current revision.