The role of TGF-b signaling in blood and lymph angiogenesis

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It is not clear how TGF-b signaling affects vascular formation in postnatal mice. To address this issue, TGF-b type II receptor conditional knockout (CKO) mice; TbRIIF/F, were crossed with Pdgfb-icreER and Prox1-CreERT2 mice in which Cre recombinase is induced in blood (BECs) and lymphatic vascular endothelial cells (LECs) by tamoxifen (Tx), respectively.When LLC cells were subcutaneously injected into TbRIIF/F; Pdgfb-icreER (TbRIIBEC-CKO), TbRII;Prox1-CreERT2 (bRIILEC-CKO) mice , both tumor and lymphangiogenesis were enhanced in CKO mice. Moreover, lung metastasis was decreased when B16 melanoma cells were injected into foot pad in both CKO mice. Blood vessels in the tumor but not in the normal tissue of TbRIIBEC-CKO mice were very leaky, indicating the poor blood circulation in tumors. Furthermore, deletion of TGF-b signaling in LEC resulted in the reduced drainage and edema. These results indicated that TGF-b signaling inhibits tumor angiogenesis and lymphangiogenesis in adults.