Chemokines in tumor angiogenesis and metastasis

Abstract

Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.

Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells

“…There are as many as 40 chemokine ligands and at least 20 corresponding receptors (1,2). Recent studies have found that the chemokines and their receptors play important roles in inflammatory responses, angiogenesis, tumor growth and metastasis (3)(4)(5). Chemokines attract and activate specific subsets of leucocytes and thus mediate chemotactic responses.…”

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

“…Recently, the function of chemokines in the process of cancer metastasis has attracted increased attention. Chemokines and their receptors are critical mediators of cell migration during routine immune surveillance, inflammation, and development (Singh et al, 2007;O'Hayre et al, 2008). One of the best studied chemokine receptors is CXCR4, primarily because of its role as a coreceptor for HIV entry as well as its ability to mediate the metastasis of a variety of cancers (Balkwill, 2004a).…”

Identification of Galectin-3-binding Protein as a Factor Secreted by Tumor Cells That Stimulates Interleukin-6 Expression in the Bone Marrow Stroma

“…Tumor cells closely interact with non-malignant cells present in the tumor stoma through a series of adhesiondependent and adhesion-independent mechanisms. Among the adhesion-independent interactions, cytokines, chemokines, and growth factors play a critical role (2,3). In this regard, the bone marrow, which is a frequent site of metastasis, provides a microenvironment that is particularly favorable to cancer progression because it is a source of hematopoietic and mesenchymal cells that produce a large number of cytokines and chemokines (4 -6).…”

“…We have previously shown that bone metastasis in human neuroblastoma is associated with activation of osteoclasts and an increase in bone resorption (12). We more recently reported (13) that activation of osteoclasts by neuroblastoma cells involves the stimulation of interleukin-6 (IL-6) 2 production by bone marrow stromal cells (BMSC), IL-6 being a potent activator of osteoclasts. A similar interaction between tumor cells and BMSC has been previously demonstrated to play a critical role in multiple myeloma, a cancer also characterized by an increase in bone destruction (14,15).…”