CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth

Abstract

CYR61 is a secreted, cysteine-rich, heparinbinding protein encoded by a growth factor-inducible immediate-early gene. Acting as an extracellular, matrix-associated signaling molecule, CYR61 promotes the adhesion of endothelial cells through interaction with the integrin ␣ V ␤ 3 and augments growth factor-induced DNA synthesis in the same cell type. In this study, we show that purified CYR61 stimulates directed migration of human microvascular endothelial cells in culture through an ␣ V ␤ 3 -dependent pathway and induces neovascularization in rat corneas. Both the chemotactic and angiogenic activities of CYR61 can be blocked by specific anti-CYR61 antibodies. Whereas most human tumor-derived cell lines tested express CYR61, the gastric adenocarcinoma cell line RF-1 does not. Expression of the CYR61 cDNA under the regulation of a constitutive promoter in RF-1 cells significantly enhances the tumorigenicity of these cells as measured by growth in immunodeficient mice, resulting in tumors that are larger and more vascularized than those produced by control RF-1 cells. Taken together, these results identify CYR61 as an angiogenic inducer that can promote tumor growth and vascularization; the results also suggest potential roles for CYR61 in physiologic and pathologic neovascularization.

Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

“…CCN1 binding to integrins stimulates cellular signaling pathways that have been shown to participate in cell proliferation [29]. Furthermore, CCN1 is known to be pro-angiogenic [30], and thus S1P may affect tumor angiogenesis through CCN1 induction. Thus, further studies will explore in more detail the roles played by CCN1 in S1P regulation of glioma cell behavior, as well other mechanisms involved in S1P regulation of glioma cell interaction with extracellular matrix, proliferation and invasion.…”

Angiogenesis in chronic inflammatory liver disease

“…49 These genes are critical for neovessel formation by the stimulation of directed migration of human microvascular ECs through an ␣v␤3 integrin-dependent pathway. 50,51 In contrast, little or no induction of MMPs or TIMPs was detected up to 4 hours following PH. Other studies, however, showed overexpression of specific MMPs at later time points.…”

CCN1 promotes vascular endothelial growth factor secretion through αvβ3 integrin receptors in breast cancer

“…CCN1 also regulates more complex processes such as angiogenesis and tumorigenesis (Planque and Perbal 2003;Babic et al 1998Babic et al , 1999Xie et al 2001a;Tsai et al 2002). Expression of CCN1 is sufficient for acquisition of hormone independence and anti-estrogen resistance in human breast cancer cells (Tsai et al 2002).…”