Expression and role of miRNA in renal cell carcinoma which resists to immunotherapy

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Fukushima Medical University
• Principal Investigator: ISHIBASHI Kei 福島県立医科大学, 医学部, 講師 (90347211)
• Co-Investigator(Kenkyū-buntansha): SHISHIDO Keiichi 福島県立医科大学, 医学部, 博士研究員 (30285035)
• Project Period (FY): 2010 – 2012
• Keywords: 腫瘍学

Research Abstract

Interferon (IFN)-α is one of the most commonly used agents in immunotherapy for patients with advanced -stage renal cell carcinoma. However, because of the drug resistance to IFN-α, its benefits are limited. In this study, we evaluated theexpression of hsa-miR-93 or SOCS3-mRNA in renal cell carcinoma cells which resists to IFN treatment. Among the renal cell carcinoma cell lines which we used in this study, 786-O cells showed resistance to IFN treatment. The expression of both hsa-miR-93 and SOCS3-mRNA was significantly higher compared with other cell lines. Suppression of hsa-miR-93 or SOCS3-mRNA induced sensitivity to IFN in 786-O cells. Especially, down regulation of SOCS3-mRNA enhanced STAT1 activation and anti-tumor activity of IFN, both in vitro and in vivo, in a human IFN- resistant RCC cell line 786-O. Because IL-6 receptor antibody blocked SOCS3 efficiently, combination therapy using an antihuman IL-6R antibody with IFN-α may represent a novel therapeutic approach for the treatment of renal cell carcinoma.

Research Products

• [Journal Article] Equally contributed Humanised antihuman IL-6R antibody with interferon inhibits renal cell carcinoma cell growth in vitro and in vivo through suppressed SOCS3 expression (2012)
  • Author(s): Oguro T, Ishibashi K, Sugino T, Hashimoto K, Tomita S, Takahashi N, Yanagida T, Haga N, Aikawa K, Suzutani T, Yamaguchi O, Kojima Y
  • Journal Title: European J Cancer Volume: 26
• [Journal Article] Equally contributed Suppression of SOCS3 increases susceptibility of renal cell carcinoma to INF-α (2011)
  • Author(s): Tomita S, Ishibashi K , Hashimoto K, Sugino T, Yanagida T, Kushida N, Shishido K, Aikawa K, Sato Y, Suzutani T, Yamaguchi O
  • Journal Title: Cancer Sci Volume: 102(1) Pages: 57-63
• [Presentation] Combination therapy with humanized antihuman IL-6R antibody and interferon-α successfully prevents the growth of 786-O renal cell carcinoma cells (2013)
  • Author(s): Kei Ishibashi, Toshiki Oguro; Shin Kumagai; Norio Takahashi; Nobuhiro Haga; Masanori Nomiya; Tomohiko Yanagida; Ken Aikawa Yoshiyuki Kojima
  • Place of Presentation: SanDiego USA
  • Year and Date: 20130504-08
• [Presentation] IL-6 and SOCS3 regulates cell proliferation in renal cell carcinoma cells AUA (2013)
  • Author(s): Kei Ishibashi, Toshiki Oguro; Shin Kumagai; Masao Kataoka; Hidenori Akaihata; Ken Aikawa; Yoshiyuki Kojima
  • Place of Presentation: SanDiego USA.
  • Year and Date: 2013-04-08
• [Presentation] Kojima TOCILIZUMAB CAN ENHANCE THE ANTI-TUMOR EFFECT OF IFN-a IN RENAL CELL CARCINOMA (2012)
  • Author(s): T. Oguro, K. Ishibashi, T. Sugino, S. Kumagai, N. Takahashi, N. Haga, T. Yanagida, K. Aikawa, O. Yamaguchi, Y.
  • Organizer: 37th ESMO Congress
  • Place of Presentation: Vienna
  • Year and Date: 20120928-1002