VEGF-B promotes cancer metastasis through a VEGF-A–independent mechanism and serves as a marker of poor prognosis for cancer patients

Cancer metastasis is responsible for a majority of the mortality in cancer patients and involves complex interactions, modulated by various factors and cytokines, between malignant and host cells. Vascular structures in solid tumors are crucial for cancer cell intravasation into the circulation. Our present work shows that VEGF-B produced by tumor cells significantly remodels tumor microvasculature, leading to leaky vascular networks that are highly permissive for tumor cell invasion. VEGF-B–promoted cancer metastasis occurs through a VEGF-A–independent mechanism. Thus, inhibition of VEGF-B should be considered an independent approach for the development of new drugs for the treatment of cancer invasion and metastasis. VEGF-B also may be considered as an independent prognostic marker for cancer metastasis.