CADM1 as a potential therapeutic target in small cell lung cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 16K09570
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Kikuchi Shinji 筑波大学, 医学医療系, 講師 (80588971)
• Project Period (FY): 2016-10-21 – 2021-03-31
• Keywords: 小細胞肺癌 / CADM1 / スプライシングバリアント / 細胞接着分子 / Liquid biopsy

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). The overall 5-year survival rate was 57.2% in patients who underwent surgical resection. A significantly good survival was observed using univariate analysis in patients with female, preoperative normal serum level of CEA, normal serum level of SCC, pR0 resection, adjuvant chemotherapy, and histological pure SCLC. We demonstrate that SCLC expresses a unique splicing variant of CADM1. This variant is almost exclusively observed in SCLC and testis. 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.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

小細胞肺癌(SCLC)は急速な進展能と高い転移能をもつ難治性腫瘍の代表であり，新たな診断法や治療法の開発が望まれている．本研究は細胞接着分子CADM1 に着目し，SCLCにおいて特異的なスプライシングバリアントを受けていることを独自に見出して研究を進めている．このCADM1バリアントは正常肺では認めないため，診断標的として有用である．また，癌の浸潤能や免疫応答に関わるCADM1の分子機構の解明は，今後の癌の細胞接着研究の重要な知見になるばかりでなく，新規の癌免疫療法の医薬品開発に直接結びつく可能性がある．この研究を通して、SCLCを患った多くの患者さんに恩恵がもたらされることを期待する．