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Schematic illustration of VEGF-B–induced tumor vessel remodeling and metastasis. The tumor-derived high VEGF-B level leads to the suppression of tumor angiogenesis and increased cell death. As a consequence, primary tumor growth is impaired, and the tumor microenvironment becomes more hypoxic. However, VEGF-B facilitates tumor cell intravasation by generating highly leaky vasculature in tumor and recruiting M2-like macrophages, thus giving rise to more severe pulmonary metastasis.
