Significance of hyaluronan in the microenvironment of prostate cancer

• Project/Area Number: 17K16771
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Hirosaki University
• Principal Investigator: Sato Tendo 弘前大学, 医学研究科, 客員研究員 (60749571)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 前立腺癌 / ヒアルロン酸 / ヒアルロニダーゼ

Outline of Final Research Achievements

Hyaluronan (HA),a major glycosaminoglycan of the extracellular matrix,is a glycosaminoglycan (GAG) composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine. HA can act as an oncogenic component of the tumor microenvironment in many human malignancies.However, clinical implication of HA on prostate cancer remains uncler. We investigated the expression of HA and TMEM2 (transmembrane 2: a cell surface hyaluronidase)in prostate cancer. We found mainly 150K HA in the surgically resected prostate cancer samples. Also, low molecular HA was dominant in the high-risk prostate cancer. Immunohistochemicla analysis showed that the low TMEM2 expression in the prostate cancer tissue. We successfully developed TMEM2 knockout mice and analyses of these mice are ongoing.

Academic Significance and Societal Importance of the Research Achievements

本研究では、前立腺癌におけるヒアルロン酸の発現意義について検討した。癌の悪性化には癌とその周囲の微小環境の関与が注目されており、組織内に大量に存在するヒアルロン酸の役割は重要である。しかし、測定が容易ではないたため、その役割は未解明であった。今回、我々は組織内の分子量分とその分解酵素の発現を検討することにより、高リスク前立腺癌におけるヒアルロン酸の分子サイズと、ヒアルロン酸分解酵素の局在を検討することができた。更にノックアウトマウスが作成されたことから、今後更なるメカニズムの解明が進むことが予想され、社会的意義は大きいものと考えられる。

Research Products

• [Journal Article] The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma. (2018)
  • Author(s): Momota M, Hatakeyama S, Tokui N, Sato T, Yamamoto H, Tobisawa Y, Yoneyama T, Yoneyama T, Hashimoto Y, Koie T, Narita S, Kawaguchi T, Ohyama C
  • Journal Title: Eur Urol Focus. Volume: 掲載確定・印刷中 Issue: 6 Pages: 001-001
  • DOI: 10.1016/j.euf.2018.03.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of bacillus Calmette-Guerin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy. (2018)
  • Author(s): Horiguchi H, Yoneyama T, Hatakeyama S, Tokui N, Sato T, Fujita N, Yamamoto H, Tobisawa Y, Yoneyama T, Hashimoto Y, Koie T, Yoshikawa K, Narita S, Kawaguchi T, Ohyama C
  • Journal Title: Med Oncol. Volume: 35 Issue: 4 Pages: 41-41
  • DOI: 10.1007/s12032-018-1102-y
  • Peer Reviewed / Open Access / Int'l Joint Research