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

Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami School of Medicine, Miami, Florida
Critical Reviews in Eukaryotic Gene Expression (Impact Factor: 1.57). 04/2013; 23(1):77-91. DOI: 10.1615/CritRevEukaryotGeneExpr.2013006905
Source: PubMed


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.

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    • "Proinflammatory cytokines, including chemokines, attack inflammatory cells and regulate hematopoietic cell migration to bone marrow or lymph nodes and neuronal migration (1,2). 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). "
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