title: Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression.
abstract: Recent studies have indicated that a high-fat diet (HFD) plays an important role in prostate cancer (PCa) progression. Palmitic acid (PA) is one of the most abundant saturated free fatty acids (FAs) and is associated with carcinogenesis. In this study, we investigated the mechanism underlying the association of dietary fat, including PA, with PCa progression. In four PCa cell lines, in vitro PA administration stimulated the expression of macrophage inhibitory cytokine 1 (MIC1), which is a divergent member of the transforming growth factor-β family. In vivo, LNCaP xenograft tumor growth, serum MIC1 levels, and FA levels in xenograft tumors were significantly higher in mice receiving an HFD containing high amounts of PA than in those receiving a low-fat diet (LFD). In addition, tumor cells with high MIC1 expression invaded to venules and lymph vessels in the LNCaP xenograft. In vitro studies showed that proliferation and invasive capacity were significantly higher in PCa cells cultured with serum from HFD-fed mice than in those cultured with the serum from LFD-fed mice. This effect was attenuated by the addition of neutralizing antibodies against MIC1, but not by isotype control antibodies. Clinically, serum MIC1 levels were significantly higher in PCa patients than in healthy controls, and higher levels were associated with higher pathological grade and obesity. In conclusion, our results indicate that an HFD containing PA may promote growth and invasiveness of PCa cells through the upregulation of MIC1 expression.
authors.affiliation: Department of Urology Research Center for Biosignal Department of Clinical Pathology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan CREST, Japan Science and Technology Agency (JST), Tokyo 102-0076, Japan.
authors.forename: Mingguo
authors.initials: M
authors.lastname: Huang
authors.forename: Shintaro
authors.initials: S
authors.lastname: Narita
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nanjo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019308:Palmitic Acid / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D055436:Growth Differentiation Factor 15; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D019308:Palmitic Acid
keywords: high-fat diet; macrophage inhibitory cytokine 1; palmitic acid; prostate cancer