CADM1 as a potential therapeutic target in small cell lung cancer

• Project/Area Number: 24790802
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Kikuchi Shinnji 筑波大学, 医学医療系, 講師 (80588971)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 小細胞肺癌 / CADM1 / スプライシングバリアント / 分子標的治療 / 予後 / 血清診断

Outline of Final Research Achievements

We investigate the roles of CADM1, a member of the immunoglobulin superfamily cell adhesion molecules, in small cell lung cancer (SCLC). Western blotting and RT-PCR analyses have revealed that CADM1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM1 is involved in anchorage-independent growth in SCLC. Then, we demonstrate that SCLC expresses a unique splicing variant of CADM1. This variant is almost exclusively observed in SCLC and testis. Interestingly, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of SCLC cells. Immunohistochemistry demonstrates that CADM1 is strongly expressed in 24 of 34 (71%) SCLC. Overexpression of CADM1 was significantly associated with poor prognosis in surgical patients. These findings suggest that CADM1 enhances the malignant features of SCLC, and could provide a molecular target specific to SCLC.

Research Products

• [Journal Article] Expression of a splicing variant of the CADM1 specific to small cell lung cancer (2012)
  • Author(s): Kikuchi S, Iwai M, Sakurai-Yageta M, Tsuboi Y, Ito T, Maruyama T, Tsuda H, Kanai Y, 0nizuka M, Sato Y, Murakami Y
  • Journal Title: Cancer Science Volume: 103 Issue: 6 Pages: 1051-1057
  • DOI: 10.1111/j.1349-7006.2012.02277.x
  • Peer Reviewed
• [Presentation] 外科的切除を受けた小細胞肺癌患者におけるCADM1過剰発現と予後との関連 (2015)
  • Author(s): 菊池 慎二
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-11-26
• [Presentation] Overexpression of CADM1 is associated with poor prognosis in small cell lung cancer (2015)
  • Author(s): Shinji Kikuchi
  • Organizer: 16th World Conference on Lung Cancer
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2015-09-06
  • Int'l Joint Research
• [Presentation] 原発性肺癌におけるCADM1発現の臨床病理学的検討 (2014)
  • Author(s): 菊池慎二
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Expression of a splicing variant of the CADM1 specific to small cell lung cancer (2013)
  • Author(s): Shinji Kikuchi
  • Organizer: 15th World Conference on Lung Cancer
  • Place of Presentation: Sydney Convention and Exhibition Centre, Sydney, Australia
• [Presentation] 細胞接着分子CADM1は小細胞肺癌において接着非依存性増殖に関与する (2012)
  • Author(s): 菊池慎二
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山コンベンションセンター（岡山）