Obesity due to a high-fat diet may promote prostate cancer metastasis, according to the results of a recent study.1

Researchers evaluated the consequences of the loss of both PTEN and PML genes in mice and found that about one-third of the mice lacking both developed lymph node metastases stemming from a primary prostate cancer.

PTEN and PML are known tumor suppressor genes which influence prostate cancer development,” said Marc C. Smaldone, MD, MSHP, FACS, a urologic oncologist at the Fox Chase Cancer Center in Philadelphia, Pennsylvania. “Studies have shown that loss of both PTEN and PML function can lead to the development of aggressive prostate cancer.”

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In this analysis, Chen et al analyzed tumors in mice to identify genes or pathways expressed in the aggressive tumors compared with indolent tumors. They found that many of the most common genes and pathways affected were involved in lipid production. Increased lipid production was, furthermore, triggered by activation of the MAPK signaling pathway, which is commonly deregulated in prostate cancer.

Based on these results, the authors considered whether higher fat intake might be linked with more aggressive prostate cancer.

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“To test this idea, they fed the tumor-prone mice a high-fat diet and investigated whether more prevalent or more aggressive prostate cancer developed in these mice,” Cory Abate-Shen, PhD, of Columbia University Medical Center in New York, New York, wrote in a commentary published in The New England Journal of Medicine.2 “The high-fat diet mimicked the effect of the loss of tumor- suppressor genes; in particular, the ‘obese’ (as defined by Chen et al.) mice had a greater tendency toward the development of metastases, which occurred not only in lymph nodes but also in soft tissues such as the lung.”

With an additional analysis, Chen et al showed that 2 months of treatment with fatostatin, an inhibitor that targets SREBP, a regulator of fat production, blocked tumor growth and distant metastasis. This suggested that reduced levels of fat in prostate cancer cells could help to improve outcomes of prostate cancer.