Interaction of tumor cells with the microenvironment

Abstract

Recent advances in tumor biology have revealed that a detailed analysis of the complex interactions of tumor cells with their adjacent microenvironment (tumor stroma) is mandatory in order to understand the various mechanisms involved in tumor growth and the development of metastasis. The mutual interactions between tumor cells and cellular and non-cellular components (extracellular matrix = ECM) of the tumor microenvironment will eventually lead to a loss of tissue homeostasis and promote tumor development and progression. Thus, interactions of genetically altered tumor cells and the ECM on the one hand and reactive non-neoplastic cells on the other hand essentially control most aspects of tumorigenesis such as epithelial-mesenchymal-transition (EMT), migration, invasion (i.e. migration through connective tissue), metastasis formation, neovascularisation, apoptosis and chemotherapeutic drug resistance. In this mini-review we will focus on these issues that were recently raised by two review articles in CCS.

Figure 1

Reciprocal interactions of tumor cells with the extracellular matrix (ECM), tumor-associated macrophages (TAM), carcinoma-associated fibroblasts (CAF), mesenchymal stem cells (MSC), and endothelial cells (EC). These interactions are mediated by direct cell-to-cell contact and/or the release of cytokines, chemokines, growth factors, matrix metalloproteases (MMPs), and ECM proteins. Eventually this results in epithelial-mesenchymal transition (EMT) of tumor cells, their migration, invasion, and dissemination to distant organs and the formation of metastases. For reasons of clarity, other stromal cell populations, e.g. lymphocytes and known interactions among different stroma cell populations are not shown.