Multi-faceted roles for CXC-chemokines in prostate cancer progression.
ABSTRACT CXC-chemokines play an essential role in co-ordinating the function of the immune system. Increasingly, these small signaling molecules are recognized in facilitating communication between multiple cell types within the tumor microenvironment. This review will summarize the role of two members of this family, CXCL12 (stromal cell derived factor-1) and CXCL8 (interleukin-8) in promoting the disease progression of prostate cancer, the most prevalent non-cutaneous cancer in men in western society and the second leading cause of death from cancer in men. Evidence for a role of these chemokines in underpinning the development and progression of this disease is supported by examination of prostate tissue and serum samples from prostate cancer patients, from biochemical and molecular investigations conducted on representative cell-based models of this disease and from observation of CXC-chemokine promoted growth and systemic dissemination of human prostate tumors in experimental in vivo models. The future potential of employing strategies to attenuate chemokine expression or alternatively to selectively block chemokine receptor signaling to effect greater long-term control or enhanced therapeutic response in this disease is also discussed.
Article: Role of chemokine network in the development and progression of ovarian cancer: a potential novel pharmacological target.[show abstract] [hide abstract]
ABSTRACT: Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development.Journal of Oncology 01/2010; 2010:426956.
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ABSTRACT: Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.Cancers. 01/2010;