Communication of tumour cells with the microenvironment

Epithelial cells are in contact with the extracellular matrix. This video shows the acinus of a mammary gland surrounded by connective tissue. Fibroblasts, macrophages and endothelial cells are embedded in the connective tissue. After the malignant transformation of a mammary gland cell, the tumor cells spread in the glandular duct and penetrate into the surrounding connective tissue. Cells and connective tissue constitute the microenvironment of the tumor. PDGF (platelet derived growth factor) and other factors produced by the tumor cells stimulate the proliferation of fibroblasts and the synthesis of components of the extracellular matrix (ECM) such as collagen. Newly formed blood vessels, which supply the tumor cells with oxygen and nutrients, run in the tumor’s microenvironment. The microenvironment is a dynamic entity that is reshaped as the tumor grows. In this context, components of the connective tissue have to be broken down and re-synthesized. TGF-b (transforming growth factor b) stimulates the production of metalloproteases in tumor fibroblasts, which cleave components of the connective tissue. Tumor-associated fibroblasts can produce the so-called scatter factor, also known as HGF (hepatocyte growth factor). Scatter factor binds to the MET receptor on the tumor cells and thus mediates their motility and invasive growth. The connective tissue of the tumor stroma can in turn affect the morphology of epithelial cells.