Chemokines in tumor progression and metastasis

Abstract

Although chemokines have been thought of primarily as leukocyte attractants, a growing body of evidence indicates that they also contribute to a number of tumor-related processes, such as tumor cell growth, angiogenesis/angiostasis, local invasion, and metastasis. The current knowledge of the possible involvement of chemokines and their receptors in these cellular events are reviewed here. The operating mechanism of chemokines in relation to metastatic processes in vivo are also discussed.

Figure 1

The chemokine receptor signaling network. Chemokine receptors can bind and activate heterotrimeric G proteins, including Gα_ißγ and Gα₁₃βγ. In a chemotaxing cell, signaling components responsible for the formation of cell polarity, directional sensing and F‐actin polymerization, such as PI3K, Rac and Cdc42, are preferentially recruited to the leading edge, whereas the mediators of actomyosin contraction, which are downstream of Rho, are recruited to the trailing edge. PTEN is excluded from the leading edge, helping to restrict PI3K signaling to the leading edge. Thus, the spatially regulated localization of signaling components plays a vital role in determining the ‘frontness’ and ‘backness’ in a chemotaxing cell. The details of the chemokine signaling pathways appear to vary slightly depending on the cellular context.