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Macrophage signaling may affect hormone resistance in prostate tumors

Interaction between prostate cancer cells and immune cells called macrophages may be a source of inflammatory signals capable of impacting the effectiveness of androgen antagonists, the most common and effective treatment for prostate cancer, according to a new study by researchers at the University of California, San Diego (UCSD) School of Medicine.

Male hormones called androgens are essential for the physiological function and growth of the prostate gland, and anti-androgen treatment, which blocks the expression of androgen target genes, is widely used for the treatment of prostate cancer. Unfortunately, most patients eventually progress to an antagonist-resistant or hormone independent form of cancer, according to David W. Rose, Ph.D., associate professor in UCSD's Department of Medicine, Division of Endocrinology and Metabolism, and Moores Cancer Center. Rose is principle investigator of the study, to be published in the Feb. 10 issue of the journal Cell.

"These findings are exciting because we have shown on the cellular level that, when the immune cells interact with the tumor cells, the result essentially negates the effect of the very drug being used to repress the tumor. If we can show the same process occurs in animals and in people, we may be able to block the "de-repression" of these genes, and develop more effective drugs to target prostate cancer tumors," Rose said.

The UCSD research team explored the possibility that external signaling from macrophages in the prostate tumor microenvironment might affect hormone resistance.Using cell biology methods, they discovered a mechanistic explanation for at least one form of resistance to androgen antagonists.

"It was of particular interest for us to determine whether a macrophage/prostate cancer cell interaction occurs, if it is a common event in prostate cancer, and whether this serves as a source of inflammatory signals capable of impacting the therapeutic effectiveness of
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Source:University of California - San Diego


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