After many research efforts and long hours spent in the laboratory, a group at the University of Colorado Cancer Center may have identified how vitamin D is connected to prostate cancer. The unifying link: inflammation.
“Inflammation is thought to drive many cancers including prostate, gastric, and colon,” said James R. Lambert, PhD, in a news release from the center. Dr. Lambert and his colleagues published their findings in The Prostate journal. As described in “Reduced Expression of GDF-15 is Associated with Atrophic Inflammatory Lesions of the Prostate,” the gene GDF-15, which is upregulated by vitamin D, is absent in cases of human prostate cancer driven by inflammation.
“GDF-15 may be a good thing in keeping prostate tissue healthy – it suppresses inflammation, which is a bad actor potentially driving prostate cancer,” explained Dr. Lambert.
The road to understanding was not as clear in the beginning. At first, Dr. Lambert’s group tested the theory that vitamin D itself could be protective against prostate cancer in general. “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.”
After the group identified GDF-15 upregulation as a downstream result of vitamin D stimulation, they looked for GDF-15 in human prostate cancer tissue samples. “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.”
Then they turned to immunohistochemistry and noticed a pattern: GDF-15 protein expression was greater in samples with inflammatory cells. It seemed GDF-15 was acting to suppress inflammation by inhibiting the transcription factor NFkB. “There’s been a lot of work on inhibiting NFkB,” said Dr. Lambert.
Since NFkB is well-studied, there may be a few new potential treatments to explore for prostate cancer. “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.”