Chemokines and Chemokine Receptors as Promoters of Prostate Cancer Growth and Progression

Abstract

Prostate cancer (CaP) is estimated to be first in incidence among cancers, with more than 240,000 new cases in 2012 in the United States. Chemokines and their receptors provide survival, proliferation, and invasion characteristics to CaP cells in both primary sites of cancer and metastatic locations. The emerging data demonstrate that many chemokines and their receptors are involved in the multistep process of CaP, leading to metastasis, and, further, that these factors act cooperatively to enhance other mechanisms of tumor cell survival, growth, and metastasis. Changes of chemokine receptor cohorts may be necessary to activate tumor-promoting signals. Chemokine receptors can activate downstream effectors, such as mitogen-activated protein kinases, by complex mechanisms of ligand-dependent activation of cryptic growth factors; guanosine triphosphate–binding, protein-coupled activation of survival kinases; or transactivation of other receptors such as ErbB family members. We describe vanguard research in which more than the classic view of chemokine receptor biology was clarified. Control of chemokines and inhibition of their receptor activation may add critical tools to reduce tumor growth, especially in chemo-hormonal refractory CaP that is both currently incurable and the most aggressive form of the disease, accounting for most of the more than 28,000 annual deaths.

Inflammation and prostate cancer: friends or foe?

“…Among the factors suspected to control prostate cancer, incidence and progression in terms of tumor cell survival, growth, angiogenesis and metastasis, chemokines, and their receptors, now intensively studied, have become a field of increasing interest and exploration [78]. It is important to notice that chemokine receptors are expressed and chemokines are produced by a variety of cells in prostate tumors, comprising not only cancer cells but also stromal cells (i.e., cancer-associated fibroblasts), endothelial cells, or infiltrating cells (i.e., macrophages, lymphocytes, NK cells, mast cells).…”

“…The most evidence of chemokine receptors endogenously expressed by cancer cells is provided for CXCR1, CXCR2, CXCR4, and CXCR7 but also other receptors such as CCR1, CCR2, CCR3, CCR5, CCR7, CCR9, CXCR3, CXCR6, CXCR5, CX3CR1 are involved in the multistep process of prostate cancer progression and metastasis [78,[87][88][89][90][91][92]. Mainly, the work on chemokines in prostate cancer has focused on not only the chemokines CXCL8, CXCL12, and CCL2 but also other chemokines such as CCL2, CCL4, CCL5, CCL9, CCL11, CCL18, CXCL1, CXCL2, CXCL5, CXCL6, CXCL12, and CXCL13 that appear to be produced by stromal cells, endothelial cells and human bone marrow endothelial cells, differentiated osteoblasts, and infiltrating leukocytes [78,[93][94][95][96][97][98][99].…”

“…Mainly, the work on chemokines in prostate cancer has focused on not only the chemokines CXCL8, CXCL12, and CCL2 but also other chemokines such as CCL2, CCL4, CCL5, CCL9, CCL11, CCL18, CXCL1, CXCL2, CXCL5, CXCL6, CXCL12, and CXCL13 that appear to be produced by stromal cells, endothelial cells and human bone marrow endothelial cells, differentiated osteoblasts, and infiltrating leukocytes [78,[93][94][95][96][97][98][99]. Chemokine receptors can activate downstream effectors by complex mechanisms of chemokine-dependent activation of cryptic growth factors including survival kinases, or transactivate other receptors such as EGFR or ErbB family members [100,101].…”

Expression of CXC chemokine receptor-4 and forkhead box 3 in neuroblastoma cells and response to chemotherapy

“…Abnormal expression of chemokines or their receptors is positively correlated with the development, progression and metastasis of tumor cells (3,4). CXC chemokine receptor-4 (CXCR4) is highly expressed on the surface of several different types of tumors (5).…”

CsCCL17, a CC chemokine of Cynoglossus semilaevis, induces leukocyte trafficking and promotes immune defense against viral infection

“…Introduction 23 24 Chemokines are a family of chemotactic cytokines that interact with seven-transmembrane 25 domain G protein-coupled receptors and play important roles in mediating leukocyte migration 26 and other biological and pathological processes, such as angiogenesis, angiostasis, hematopoiesis, 27 cell proliferation, tumor growth, apoptosis, and immune defense [1][2][3]. Chemokines are small 28 extracellular proteins that are ~8-10 kDa in size, which generally have four highly conserved 29 cysteine residues that are pivotal to form disulphide linkages and the tertiary structure [4].…”