Role of Microenvironment on Gene Expression, Angiogenesis and Microvascular Function in Tumors

Abstract

Solid tumors are organ-like entities. In addition to neoplastic cells, they consist of non-transformed host stromal cells such as endothelial cells, fibroblasts and inflammatory cells. All of these cells are embedded in a characteristic extracellular matrix and are surrounded by specific molecular and metabolic microenvironments. Blood and lymphatic vessels, which are important for maintaining the homeostasis of living organisms, are compromised in solid tumors, causing various physiological barriers to the delivery of therapeutic agents to tumors in sufficient quantity and under optimal conditions. There is a growing body of evidence that stromal cells are not quiescent bystanders; instead, they significantly influence the pathophysiology of tumors. Both stromal cells and tumor cells participate in the formation of this milieu, and the microenvironment, which includes the expression of positive and negative regulators of angiogenesis, influences the biology of these cells. Any of these factors — tumor cells, stromal cells, and the local microenvironment of particular organs — may vary during treatment and may influence the efficiency of various treatment modalities. Therefore, stromal cells and the tumor microenvironment offer novel targets for tumor detection and treatment. A better understanding of host-tumor interaction and formation, as well as of the function of blood and lymphatic vessels in tumors in different microenvironments, is warranted in order to facilitate the development of such strategies.