Fig. 2.

The role of angiocrine endothelium in promoting tumorigenicity. ECs were initially known for their role in tumor angiogenesis. Emerging evidence shows an angiocrine role for tumor endothelium in inducing tumor growth and survival advantages through production of angiocrine factors. Several angiocrine factors such as VEGF, bFGF, IL-6, IL-8, TGFβ, PDGFβ, Jag1, and Endothelin, have been shown to enhance tumor cell proliferation. Also, a role for angiocrine factors is implicated in increased proliferation of cancer stem and progenitor cells in brain tumor (BDNF, PEDF, BMP2, and BMP4), head and neck cancer (EGF), and breast cancer (Jag1). Recent evidence demonstrates the participation of angiocrine endothelium in tumor immune tolerance. Angiocrine molecules such as ICAM-1, VCAM, and Selectin regulate the transmigration of lymphocytes through the lymphatic vessels. Endothelial bFGF plays a role in stimulation of leukocyte infiltration. Some secretory chemokine (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) affect T cell infiltration to the tumor site. ECs are also capable of over-expressing specific molecules such as ET_BR to provide a barrier for tumor-infiltrating lymphocytes. Additional mechanisms include escape from immune response regulated by Tim-3 or FasL. A recent angiocrine function for endothelial-derived thrombospondin-1 is defined in induction of tumor dormancy. Besides, endothelial FGF2 is capable of triggering resistance of anti-angiogenic drugs through activation of FGF2/FGFR1 loop. Quite notably, some angiocrine elements may have multiple functions in tumor expansion. Table 1 provides distinct functional information for the viewers