Abstract B20: Activin receptor-like kinase 1 complexes with endoglin in TGFß-mediated signaling in angiogenesis

• Published in: Molecular cancer therapeutics 2015-12, Vol.14 (12_Supplement_1), p.B20-B20
• Main Authors: Hawker, James, Varacallo, Patricia, Duffy, Iain
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1538-8514.TUMANG15-B20

Background: Activin Receptor-Like Kinase 1 (ALK1), a type I transforming growth factor (TGFß) family receptor, and endoglin, a type III receptor, are expressed in endothelial cells (EC) and involved in angiogenesis. Control of angiogenesis is critical in diseases such as cancer. Four ligands, TGFß, activin, bone morphogenetic protein 9 (BMP-9), and BMP-10, have been shown to bind ALK-1. Thus angiogenesis may be mediated by different combinations of ligands and receptors. Purpose: We investigated the role of TGFß and ALK-1 in tube formation. We also screened EC and also cancer cell lines for expression of various TGFß family receptors to begin to address which ligands and receptors are involved in angiogenesis and endothelial-tumor interactions,. Results: We also show that fibroblast growth factor 2 (FGF-2) + TGFß increase ALK-1 but not ALK 5 type I receptor expression in endothelial cells after tube formation. We show data that the type I receptor Activin-Like Kinase 1 and the co-receptor endoglin can signal in endothelial cells via the TGFß ligand. Antisense RNA that targets ALK 1 (and also ALK5) also disrupts tube formation. We further show that endogenous activin binds ALK 1 and can be displaced by exogenous TGFß. This suggests it may function to regulate control of ALK 1 activation. Further, ALK-1 and endoglin may also be involved in cell-cell interactions between endothelial and other cells. Thus we screened endothelial and cancer cells for TGFß family receptor expression by RT-PCR. Endothelial cells show similar expression of ALK-1, ALK-5, and endoglin and lower expression of BMP receptor II and TGFßRII. Cancer cells show much lower expression of type II receptors. Citation Format: James Hawker, Patricia Varacallo, Iain Duffy. Activin receptor-like kinase 1 complexes with endoglin in TGFß-mediated signaling in angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B20.