Study examines link between inflammation, prostate Ca

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Researchers at UCLA have discovered a previously unrecognized type of progenitor cell in inflamed areas of the prostate that have the ability to initiate cancer in response to genetic changes.

New research suggests inflammation increases overall risk for prostate cancer by increasing the available pool of progenitor cells that can develop into the disease.

While progenitor cells are targets for cancer initiation and are common in the basal layer of the human prostate and rare in the luminal layer, a group of researchers at UCLA have discovered a previously unrecognized type of progenitor cell in inflamed areas of the gland that have the ability to initiate prostate cancer in response to genetic changes.

“We went on a search to find those rare progenitor cells in the luminal layer and came across these luminal cells which lack expression of the CD38 molecule (CD38-low), even though most luminal cells express high levels of CD38,” senior author Andrew Goldstein, PhD, of UCLA, told Urology Times. “Within the pool of luminal cells that do not express CD38, there were five times as many progenitor cells that could expand and divide as compared to the pool of luminal cells expressing high levels of CD38.”

While these CD38-low luminal progenitor cells were rare in most regions of the prostate, they were clustered in regions immediately adjacent to inflammation, and the study suggests this inflammation increases an overall risk for prostate cancer.

The study, published in Cell Reports (2016; 17:2596-606), entailed utilizing fresh patient prostate tissue from areas without cancer that were determined by the pathology department to be not needed for diagnostic purposes. The authors dissociated that benign human prostate tissue to single cells and used Fluorescence Activated Cell Sorting to isolate different types of epithelial cells and test their capacity to grow in culture or in mice.

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“We found that CD38-low luminal progenitor cells were capable of responding to genetic changes and generating aggressive human prostate cancer when transplanted into mice. Therefore, inflammation is associated with an increased number of progenitor cells that are targets for initiating cancer,” Dr. Goldstein said.

Next: A surprising result

When they looked to see whether these CD38-low progenitor cells were present in prostate cancer, the authors found a surprising result.

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“The tumors which had the lowest expression of CD38 were the most aggressive, most likely to recur and metastasize. In contrast, tumors with the highest expression of CD38 had a much better prognosis, less likely to metastasize. We hypothesize that these aggressive tumors, which do not express CD38, may arise in progenitor cells that do not express CD38,” Dr. Goldstein said.

The researchers now believe that chronic inflammation increases the risk for prostate cancer because it increases the pool of cells that are capable of responding to genetic changes and developing into prostate cancer. With that theory out there, the UCLA team is hoping to understand what gives these CD38-low luminal progenitor cells from regions with inflammation the ability to proliferate and respond to genetic alterations.

“We also want to determine what role the CD38 molecule plays in the development of prostate cancer, given that luminal cells with low CD38 are more proliferative and tumors with low CD38 are more metastatic than their counterparts expressing high levels of CD38,” Dr. Goldstein said. “More work should be done to understand the causes of chronic inflammation in the prostate, so that approaches can be taken to avoid these causes in younger men or treat the chronic inflammation as a precursor stage during the development of prostate cancer.”