A digest on the role of the tumor microenvironment in gastrointestinal cancers

Abstract

Experimental studies and analyses of clinical material have convincingly demonstrated that tumor formation and progression occurs through a concerted action of malignant cells and the surrounding microenvironment of the tumor stroma. The tumor microenvironment is comprised of various cell types like fibroblasts, immune cells, vascular cells and bone-marrow-derived cells embedded in the extracellular matrix. This review, focusing on recent findings in the context of gastrointestinal tumors, introduces the different stromal cell types and delineates their contributions to cancer initiation, growth and metastasis. By selected examples we also present how the tumor microenvironment is emerging as a promising target for therapeutic intervention.

Keywords: Therapy; Tumor microenvironment; Tumor stroma.

Fig. 1

Fueling tumorigenesis and cancer cell spreading. The close interaction of cancer cells with its microenvironment-composed of cancer-associated fibroblasts (CAF), immune cells, endothelial and lymphatic cells-results in the production and release of a multitude of soluble factors and constituents of the extracellular matrix (ECM). These molecules in turn have mitogenic, pro-migratory and pro-invasive or chemoattractant properties thereby stimulating e.g. cancer cell growth, invasion and metastasis, vessel formation or the recruitment of immune cells and precursor cells such as bone-marrow-derived cells (BMDC). The figure highlights more recently described molecules in different GI cancer