Vitamin D, prostate Ca: Study points to missing link

Inflammation may be the missing link between vitamin D and prostate cancer, new study findings from the University of Colorado Cancer Center in Denver suggest.

Specifically, the study shows that the gene GDF-15, known to be upregulated by vitamin D, is notably absent in samples of human prostate cancer driven by inflammation. The study was recently published in Prostate.

“When you take vitamin D and put it on prostate cancer cells, it inhibits their growth. But it hasn’t been proven as an anti-cancer agent. We wanted to understand what genes vitamin D is turning on or off in prostate cancer to offer new targets,” said first author James R. Lambert, PhD, who worked on the study with Scott Lucia, MD, and colleagues.

Since demonstrating that vitamin D upregulates the expression of GDF-15, the researchers set out to determine if this gene might be a mechanism through which vitamin D works in prostate cancer. Initially, the answer appeared to be no.

“We thought there might be high levels of GDF-15 in normal tissue and low levels in prostate cancer, but we found that in a large cohort of human prostate tissue samples, expression of GDF-15 did not track with either normal or cancerous prostate tissue,” Dr. Lambert said in a University of Colorado news release.

But the team then noticed that GDF-15 was uniformly low in samples of prostate tissue that contained inflammation.

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“Inflammation is thought to drive many cancers, including prostate, gastric, and colon. Therefore, GDF-15 may be a good thing in keeping prostate tissue healthy; it suppresses inflammation, which is a bad actor potentially driving prostate cancer,” Dr. Lambert said.

The researchers used a sophisticated computer algorithm to analyze immunohistochemical (IHC) data. With this new technique, they were able to quantify the expression of the GDF-15 protein and inflammatory cells by IHC staining on slides taken from human prostate samples.

Also encouraging is that the gene GDF-15 was shown to suppress inflammation by inhibiting another target, NFkB. NFkB has been the focus of previous studies in which it has been shown to promote inflammation and contribute to tumor formation and growth, but researchers have previously been unable to inhibit NFkB to decrease its tumor-promoting behavior.

“There’s been a lot of work on inhibiting NFkB,” said Dr. Lambert. “Now from this starting point of vitamin D in prostate cancer, we’ve come a long way toward understanding how we might use GDF-15 to target NFkB, which may have implications in cancer types far beyond prostate.”

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