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Prostate cancer

Obesity and inflammation associated with prostate cancer

(Credit: Obesity Action Coalition)
Inflammatory drugs, such as celecoxib, may have clinical benefits for obese patients with prostate cancer

It is known that a high-fat diet (HFD) leads to obesity and chronic inflammation, and studies conducted on mice have shown that HFD could be associated with progression and survival of prostate cancer, according to researchers from a team of Osaka University, Osaka, Japan. In human studies, inflammation and immune cells are also linked to prostate cancer.

While much is known about how HFD increases serum proinflammatory cytokines (small proteins that are important in cell signalling), it remains unclear whether tumour progression resulted from these cytokines. In this latest study, ‘High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling’, reported in Clinical Cancer Research, the investigators successfully determined the mechanisms of the associations of prostate cancer with inflammation and immune responses.

"We administered an HFD and anti-inflammatory drug celecoxib to a genetically engineered autochthonous mouse model, which corresponds to somatic mutations of human prostate cancer model mice," explained study lead author, Dr Takuji Hayashi. "Tumour growth was evaluated by tumour weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Further, cytokines that correlated with tumour growth were identified."

The researchers found that HFD accelerated tumour growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and the ratio of M2/M1 macrophage, a major type of immune cells, in the model mice. MDSCs regulate immune responses and tissue repair in healthy individuals and the population rapidly expands during inflammation, infection and cancer. Celecoxib was observed to suppress tumour growth and reduced local MDSCs and M2/M1 macrophage ratio in HFD-fed mic.

Administration of antibody specific to the receptor of cytokine IL6 suppressed tumour growth and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. In response to cytokines and growth factors, STAT3 is phosphorylated (to become pSTAT3) and translocated to the cell nucleus, where it acts as a gene transcription activator. The tumour-infiltrating CD11b-positive cell count was also found to be significantly higher in prostatectomy specimens of obese patients than in those of non-obese patients with prostate cancer.

"Taken together, our results suggest that HFD-induced prostate cancer growth via IL6 signalling could also exist in obese humans," said corresponding author, Dr Kazutoshi Fujita. "Anti-inflammatory drugs, such as celecoxib, may have clinical benefits for obese patients with prostate cancer. Additionally, an improvement of dietary habits or an intake of analgesic may lead to prophylaxis and contribute to the treatment of prostate cancer."

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