Extracellular matrix proteins and tumor angiogenesis

Abstract

Tumor development is a complex process that relies on interaction and communication between a number of cellular compartments. Much of the mass of a solid tumor is comprised of the stroma which is richly invested with extracellular matrix. Within this matrix are a host of matricellular proteins that regulate the expression and function of a myriad of proteins that regulate tumorigenic processes. One of the processes that is vital to tumor growth and progression is angiogenesis, or the formation of new blood vessels from preexisting vasculature. Within the extracellular matrix are structural proteins, a host of proteases, and resident pro- and antiangiogenic factors that control tumor angiogenesis in a tightly regulated fashion. This paper discusses the role that the extracellular matrix and ECM proteins play in the regulation of tumor angiogenesis.

Figure 1

Summary of various extracellular matrix (ECM) proteins that are involved in tumour angiogenesis. Activation of tumor-derived ECM proteins permits communication between the tumor and its surrounding microenvironment. Regulating of angiogenesis can be directly through MMP activation and degradation of the ECM or through and indirect mechanism. This involves interactions between various ECM proteins and pro or antiangiogenic growth factors in order to alter angiogenesis. Ultimately, expression of the proangiogenic growth factor can influence the angiogenic phenotype and determine whether vascular sprouting occurs in order to provide the tumor with the necessary nutrients to survive.