The Role of Chemokines and their Receptors in Tumor Progression and Invasion: Potential New Targets of Biological Therapy

Paola      Allavena; Federica      Marchesi; Alberto      Mantovani

Abstract

Chemotactic cytokines (chemokines) are a family of small proteins inducing directed cell migration (chemotaxis), via specific G-protein coupled receptors. Initially described as molecules regulating leukocyte recruitment at sites of inflammation, in the last decade, it has become increasingly clear that chemokines mediate several other functions and therefore are more than simple traffick controllers. Chemokines are produced by many different cell types, including tumor cells. Indeed, tumors are major producer of chemokines and have represented an invaluable source for their identification and characterization. In the tumor microenvironment chemokines are crucial regulators of the levels of tumorinfiltrating leukocytes. In addition, these mediators control a variety of biological activities, such as production and deposition of collagen, activation of matrix-digesting enzymes, stimulation of cell growth, inhibition of apoptosis and promotion of neo-angiogenesis. The expression of chemokines, therefore, is of potential advantage for tumor cells and may endow them with enhanced ability to proliferate and disseminate. The complex network of chemokines and their receptors in the tumor microenvironment is currently the object of an intense investigation aimed at targeting these molecules for therapeutic interventions.

Keywords: chemokines, chemokine receptors, chemotaxis, tumor-associated macrophages, tumor-infiltrating leukocytes, tumor stroma, angiogenesis, matrix-metalloproteases, tumor survival, metastasis