Mechanisms of high-fat induced prostate cancer progression through Monocyte Chemotactic Protein-1 secreted by adipose tissue

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791739
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: SHINTARO Narita 秋田大学, 医学部, 講師 (40396552)
• Project Period (FY): 2011 – 2012
• Keywords: 前立腺癌 / 肥満 / 高脂肪 / Monocyte Chemotactic Protein-1 / MCP-1

Research Abstract

We investigated the effects of different diets on prostate cancer cell growth and the relevant circulating factors including serum insulin, growth factors, and inflammatory cytokines using the in vivo and ex vivo model. The tumor growth of prostate cancer LNCaP xenograft was significantly higher in the HFD group than in the HCD and control diet (CD) groups. The mean level of the serum monocyte chemoattractant protein-1 (MCP-1) in the HFD group was significantly higher than that in the HCD and CD groups. The mRNA levels of CC chemokine receptor 2 (CCR2), which is an MCP-1 receptor, and the expression of activated Akt were the highest in the HFD group. Furthermore, serum from HFD-fed mice enhanced the proliferation of two PCa cells and CCR2 knockdown inhibited HFD-induced proliferation of LNCaP cells. In conclusion, an HFD enhanced prostate cancer cell growth more strongly than an HCD or CD. MCP-1/CCR2 signaling may be involved in an HFD-induced prostate cancer progression.

Research Products

• [Journal Article] A high-fat diet enhances proliferation of prostate cancer cells and activates MCP-1/CCR2 signaling (2012)
  • Author(s): Huang, M., Narita, S., Numakura, K., Tsuruta, H., Saito, M., Inoue, T., Horikawa, Y., Tsuchiya, N.and Habuchi, T.
  • Journal Title: Prostate Volume: 72 Pages: 1779-1788
• [Journal Article] Overexpression of Fn14 promotes Androgen independent prostate cancer progression through MMP-9 and correlates with poor treatment outcome (2011)
  • Author(s): Huang, M., Narita, S., Tsuchiya, N., Ma Z., Numakura, K., Obara, T., Tsuruta, H., Saito, M., Inoue, T., Horikawa, Y., Satoh, S. and Habuchi, T.
  • Journal Title: Carcinogenesis. Volume: 32 Pages: 1589-96
• [Presentation] 前立腺癌進展における長鎖脂肪酸パルミチンの役割 (2012)
  • Author(s): 黄明国、成田伸太郎,井上高光,土谷順彦,佐藤滋,羽渕友則
  • Organizer: 第71回日本癌学会・総会
  • Place of Presentation: 札幌
  • Year and Date: 20120900
• [Presentation] Stimulation of macrophage inhibitory cytokine-1 by palmitic acid activates prostate cancer cell invasiveness (2012)
  • Author(s): Mingguro, H., Narita, S., Maita, S., Numakura, K., Obara, T., Inoue, T., Horikawa, Y., Satoh, S.and Habuchi, T.
  • Organizer: The 107th annual meeting of the American Urological Association
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20120400
• [Presentation] Prostate cancer progression under high fat diet is enhanced by the MCP-1/CCR2 signaling (2011)
  • Author(s): Huang, M., Narita, S., Numakura, K., Tsuruta, H., Saito, M., Inoue, T., Horikawa, Y., Tsuchiya, N., Habuchi, T.
  • Organizer: The 106th Annunal Meeting of the American Urological Association
  • Place of Presentation: Washisnton DC, USA
  • Year and Date: 20110500
• [Presentation] サイトカインシグナルを介した高脂肪食摂取下の前立腺癌増殖機序の解明(ヤングリサーチグラント受賞者記念講演) (2011)
  • Author(s): 成田伸太郎
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20110400