A recently published paper from the Beth Israel Deaconess Medical Center (BIDMC) revealed new insights on how obesity is associated with prostate cancer. The research, published in the journals Nature Genetics and Nature Communications, linked eating a high-fat meal, together with genetic factors, to the promotion of metastasis (the spread of cancer from its initial site to other areas in the body), particularly for indolent tumors such as those found in the prostate.
"Although it is widely postulated that a Western diet can promote prostate cancer progression, direct evidence supporting a strong association between dietary lipids and prostate cancer has been lacking," according to Dr. Ming Chen, one of the authors of the study in BIDMC.
For the study, researchers evaluated the tumor-suppression properties of PTEN (phosphatase and tensin homolog) and its relation to prostate cancer. PTEN is a gene that can inhibit rapid reproduction, longevity, and growth of tumor cells. However, PTEN is also lost when cancer progresses. In the study, about 70 percent of primary prostate tumors is also accompanied by a partial loss of PTEN, and its complete loss is correlated to metastatic prostate disease. However, in vivo studies suggest otherwise.
Recent genomic data revealed that PML, another gene for suppressing tumor growth, was discovered in prostate tumors that have not yet spread. However, this was also lost when these became metastatic prostate tumors. When the tumors that do not have PTEN and PML were reviewed, the cell's lipogenic – or fat production – switch produced "abnormally high amounts of fat."
"It was as though we'd found the tumors' lipogenic, or fat production, switch," reported Dr. Pier Paolo Pandolfi, a senior author of the study. "The implication is, if there's a switch, maybe there's a drug with which we can block this switch and maybe we can prevent metastasis or even cure metastatic prostate cancer."
Aside from these factors, the research team found that a high-fat diet, typical in Western countries, contributed to the progression of metastatic tumors. While epidemiological data traces many cancer types, including prostate cancer, to dietary fats, incidence and mortality rates for cancer in the U.S. are higher than in countries that have diets with a lower fat content.
Through in vivo testing, the team discovered that mice that were fed with a diet high in saturated fats (like those found in fast food joints) developed aggressive and metastatic tumors.
The findings could progress to more accurate and predictive mouse models when dealing with metastatic prostate cancer. This could also help with the discovery of more efficient ways of managing and treating the disease, as well as guide health professionals to make a better prognosis for at-risk patients who do not have PTEN and PML genes.
"The progression of cancer to the metastatic stage represents a pivotal event that influences patient outcomes and the therapeutic options available to patients," Dr. Pandolfi explained. "Our data provide a strong genetic foundation for the mechanisms underlying metastatic progression, and we also demonstrated how environmental factors can boost these mechanisms to promote progression from primary to advanced metastatic cancer."
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