Inflammatory chemokines and metastasis—tracing the accessory

Abstract

The tumor microenvironment consists of stromal cells and leukocytes that contribute to cancer progression. Cross-talk between tumor cells and their microenvironment is facilitated by a variety of soluble factors, including growth factors, cytokines such as chemokines. Due to a wide expression of chemokine receptors on cells in the tumor microenvironment, including tumor cells, chemokines affect various processes such as leukocyte recruitment, angiogenesis, tumor cell survival, tumor cell adhesion, proliferation, vascular permeability, immune suppression, invasion and metastasis. Inflammatory chemokines are instrumental players in cancer-related inflammation and significantly contribute to numerous steps during metastasis. Recruitment of myeloid-derived cells to metastatic sites is mainly mediated by the inflammatory chemokines CCL2 and CCL5. Tumor cell homing and extravasation from the circulation in distant organs are also regulated by inflammatory chemokines. Recent experimental evidence demonstrated that besides leukocyte recruitment, tumor cell-derived CCL2 directly activated endothelial cells and together with monocytes facilitated tumor cell extravasation, in a CCL2-and CCL5-dependent manner. Furthermore, CX3CL1 expression in the bone facilitated metastasis of CX3CR1 expressing tumor cells to this site. Current findings in preclinical models strongly suggest that inflammatory chemokines play an important role during metastasis and targeting of the chemokine axis might have a therapeutic potential. 2

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

“…Although the higher permeability in the BMi microenvironment is likely due to a combination of factors, it may also contribute to the increase in extravasation. Indeed, matrix-specific cell-secreted chemokines can both generate molecular gradients affecting cancer cell transendothelial migration (39) and alter endothelial permeability (40). Of particular note is the increase in microvasculature permeability when adenosine is added.…”

Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion

“…In this regard, chemokines are emerging as key mediators in the homing of cancer cells to metastatic sites and in the recruitment of different cell types to establish tumor microenvironment, facilitating tumor-associated angiogenesis, and metastasis [38,39]. Brain tumor is one of the leading causes of cancer-related death worldwide.…”

Serum ENA78/CXCL5, SDF-1/CXCL12, and their combinations as potential biomarkers for prediction of the presence and distant metastasis of primary gastric cancer

“…They have been suggested to play multiple roles in the development and progression of various tumors [6,7]. Epithelial-derived neutrophil-activating peptide-78 (ENA78), also known as C-X-C motif chemokine 5 (CXCL5), is a strong neutrophil chemoattractant [8].…”