Prostate Biopsies may cause Metastases

Inflammation caused by Biopsy may be involved in prostate cancer metastasis

A report published online on March 19, 2007 in the journal Nature described the findings of University of California San Diego researchers that the inflammation associated with the immune system's attack on prostate tumors could be involved in their metastasis. It has been hypothesized that genetic changes within the cancer cell result in metastasis, but this does not explain metastases that occur years after the primary tumor.

Working with a mouse model of prostate cancer, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, Michael Karin, PhD, and his colleagues discovered a signaling pathway that increased prostate tumor metastases. They found that a cytokine called RANK ligand, produced by inflammatory cells, initiates a chain reaction in which a protein kinase known as IKKa is activated to enter the cancer cell nucleus and reduce the expression of the antimetastatic gene Maspin.

"An excellent inverse correlation between IKKa activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKa in their nuclei and express little or no Maspin," Dr Karin stated. "Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKa."

"Our findings suggest that promoting inflammation of the cancerous tissue, for instance, by performing prostate biopsies, may, ironically, hasten progression of metastasis," Dr Karin observed. "We have shown that proteins produced by inflammatory cells are the 'smoking gun' behind prostate cancer metastasis. The next step is to completely indict one of them."

Research team member Steven L. Gonias, MD, PhD, added, "This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive."