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Researchers Find Missing Link Between Vitamin D and Prostate Cancer

Absence of single gene drives inflammation

A University of Colorado Cancer Center study published in the journal Prostate offers evidence that inflammation may be the link between vitamin D and prostate cancer. Specifically, the study shows that the gene GDF-15, known to be up-regulated by vitamin D, is notably absent in samples of human prostate cancer driven by inflammation.

“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 [treatment] targets,” said lead investigator James R. Lambert, PhD.

Since demonstrating that vitamin D up-regulates the expression of GDF-15, Lambert and his colleagues wondered whether this gene might be a mechanism through which vitamin D works in prostate cancer. Initially, it seemed as if the answer was 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,” Lambert said.

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

“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,” Lambert explained.

The study used a sophisticated computer algorithm to analyze immunohistochemical data, a task that had been done subjectively by pathologists in previous studies. With this new technique, Lambert and his colleagues were able to quantify the expression of the GDF-15 protein and inflammatory cells by IHC staining on slides taken from human prostate samples.

The GDF-15 gene was shown to suppress inflammation by inhibiting another target, nuclear factor kB (NFkB), a transcription factor discovered in 1986. This target has been the focus of many previous studies, in which it was shown to promote inflammation and to contribute to tumor formation and growth. However, researchers have been unable to “drug” NFkB to reduce its tumor-promoting behavior.

“There’s been a lot of work on inhibiting NFkB,” Lambert said. “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.”

Source: University of Colorado Cancer Center; October 22, 2014.

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