TGFß family receptors ALK‐1, ALK‐5, Endoglin, TGFßRII, and BMPRII are expressed on endothelial cells and show differing biological responses to different TGFß family ligands

Abstract

Transforming growth factor (TGFß) family and their receptors have been shown to be involved in angiogenesis. Angiogenesis is an important process occurring in tumors. TGFß family members that may act on endothelial cells are TGFß1, Bone Morphogenetic protein 9 (BMP-9), and Activin A. They all can signal through the type I receptor Activin-Like Kinase 1 (ALK-1). We show that endothelial cells express ALK-1, endoglin, Activin Receptor-Like Kinase 5 (ALK-5) by quantitative RT- PCR. They also express the type II receptors TGFßRII and BMPRII. In experiments we show that BMP-9 appears to increase human umbilical vein endothelial cell (HUVEC) proliferation while TGFß blocks proliferation of endothelial cells. TGFß can signal through both ALK-1 and ALK-5 while BMP-9 binds only ALK-1. Moreover we also report that endothelial cells express Activin A growth factor by RT-PCR and are testing the effects of this growth factor on endothelial cell proliferation as well. We are exploring how different growth factors can elicit different biological responses while signaling through the same receptors. The difference may depend on which type II receptor is recruited to the signaling complex. Understanding the ligand-receptor relationships and effects will provide insight into the process of angiogenesis in health and diseases including cancer.