Integrins in tumor angiogenesis and lymphangiogenesis - PubMed (original) (raw)

Integrins in tumor angiogenesis and lymphangiogenesis

Philippe Foubert et al. Methods Mol Biol. 2012.

Abstract

Angiogenesis, the formation of new blood vessel, plays an important role for the growth and metastasis of malignant tumors. The recent identification of specific growth factors for lymphatic vessels and of new lymphatic-specific markers provided evidence for an active role of the lymphatic system during the tumor growth and metastasis processes. Tumor lymphangiogenesis has been shown to play a role in promoting tumor growth and metastasis of tumor cells to distant sites. Integrins play keys roles in the regulation of angiogenesis and lymphangiogenesis during normal development and several diseases. Indeed, integrins control vascular and lymphatic endothelial cell adhesion, migration, and survival. Importantly, integrin inhibitors can block angiogenesis and lymphangiogenesis. In this chapter, we will highlight the role of integrins during angiogenesis and lymphangiogenesis as well as the function of individual integrins during vascular development, postnatal angiogenesis, and lymphangiogenesis. We discuss the role of integrins as potential therapeutic targets for the control of tumor angiogenesis, lymphangiogenesis, and metastatic spread in the treatment of cancer. We also describe methods to analyze expression and function of integrins during angiogenesis and lymphangiogenesis.

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Figures

Figure 1

Figure 1

The integrin family of adhesion of adhesion receptors and their ligands. There are 18 α and 8 β subunits which assemble to form 24 different heterodimers. Heterodimer composition confers ligand specificity. The main ligands for integrins in the extracellular space are extracellular matrix proteins, such as laminin, collagen, vitronectin and fibronectin. Moreover, integrins can also bind cellular counter-receptors (VCAM-1 or ICAM-1) and soluble molecules (fibrinogen).

Figure 2

Figure 2

Role of integrins in tumor angiogenesis and lymphangiogenesis. The tumor microenvironment activates or upregulates expression of integrins such as α1β1, α2β1, α4β1, α5β1 and αvβ3 on blood vessels and α1β1, α2β1, α4β1 and α9β1 on lymphatic vessels. Then, these integrins promote endothelial and lymphatic cells migration and survival during invasion of tumor tissue. Angiogenesis and lymphangiogenesis promote metastasis to local and distant organ such as lung.

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