High‐fat diet promotes prostate cancer growth through histamine signaling. Issue 4 (26th April 2022)

• Record Type: Journal Article
• Authors: Matsushita, Makoto; Fujita, Kazutoshi; Hatano, Koji; Hayashi, Takuji; Kayama, Hisako; Motooka, Daisuke; Hase, Hiroaki; Yamamoto, Akinaru; Uemura, Toshihiko; Yamamichi, Gaku; Tomiyama, Eisuke; Koh, Yoko; Kato, Taigo; Kawashima, Atsunari; Uemura, Motohide; Nojima, Satoshi; Imamura, Ryoichi; Mubeen, Aysha; Netto, George J.; Tsujikawa, Kazutake; Nakamura, Shota; Takeda, Kiyoshi; Morii, Eiichi; Nonomura, Norio
• Is Part Of: International journal of cancer. Volume 151:Issue 4(2022)
• Page Start: 623
• Page End: 636
• Publication Date: 2022-04-26
• Subjects: gut microbiome -- high‐fat diet -- histamine -- lipopolysaccharide -- prostate cancer; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.34028
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Western high‐fat diets (HFD) are regarded as a major risk factor for prostate cancer (PCa). Using prostate‐specific Pten ‐knockout mice as a PCa model, we previously reported that HFD promoted inflammatory PCa growth. The composition of the gut microbiota changes under the influence of diet exert various effects on the host through immunological mechanisms. Herein, we investigated the etiology of HFD‐induced inflammatory cancer growth and the involvement of the gut microbiome. The expression of Hdc, the gene responsible for histamine biosynthesis, and histamine levels were upregulated in large prostate tumors of HFD‐fed mice, and the number of mast cells increased around the tumor foci. Administration of fexofenadine, a histamine H1 receptor antagonist, suppressed tumor growth in HFD‐fed mice by reducing the number of myeloid‐derived suppressor cells and suppressing IL6/STAT3 signaling. HFD intake induced gut dysbiosis, resulting in the elevation of serum lipopolysaccharide (LPS) levels. Intraperitoneal injection of LPS increased Hdc expression in PCa. Inhibition of LPS/Toll‐like receptor 4 signaling suppressed HFD‐induced tumor growth. The number of mast cells increased around the cancer foci in total prostatectomy specimens of severely obese patients. In conclusion, HFD promotes PCa growth through histamine signaling via mast cells. Dietary high‐fat induced gut dysbiosis might be involved in the inflammatory cancer growth. Abstract : What's new? High‐fat diets consisting of large amounts of animal fat are linked to an increased risk of prostate cancer, an association attributed in part to the ability of excess fat to induce inflammation in prostate immune cells. While the mechanism behind this phenomenon is unknown, the present study shows that high animal fat intake promotes prostate cancer growth via histamine signaling by mast cells. In addition, in mice, gut dysbiosis induced by a high‐fat diet resulted in elevated lipopolysaccharide (LPS) levels, whereas inhibition of LPS signaling suppressed tumor growth. The findings reveal novel links between fat intake and inflammation in cancer.