Is sphingolipid of the cell membrane involved in invasion and metastasis of non-adenocarcinoma of the lung?

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: UEDA Yoshimichi 金沢医科大学, 医学部, 教授 (50271375)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肺扁平上皮癌 / 細胞膜スフィンゴ脂質 / 上皮間葉移行 / sphingosin kinase 1 / 肺胞腔内進展 / 浸潤・転移

Outline of Final Research Achievements

To establish a novel therapeutic strategy against invasion and metastasis of squamous cell carcinoma (SCC) of the lung, we investigated expression of sphingosine kinase (SK) 1 and its receptors (SIPR 1-5), which had been reported to show novel functions relating to the progression of cancer, and found the followings: 1. Overexpression of SK1 was demonstrated in squamous cell carcinoma tissue by western; 2. IHC study localized the expression of SK1 in the invasion front of SCC, showing association with the expression of molecules related to epithelial mesenchymal transition (EMT) and to invasion and metastasis; 3. Spreading through air space region showed reduction of SK1 as well as EMT- and invasion-related molecules; 4. The expression of SK1 as well as its receptors showed no correlation with prognosis of patients with SCC.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

本研究は、肺腺癌と比べ分子標的治療の開発が停滞している肺扁平上皮癌・小細胞癌に対する浸潤・転移の新たな制御法の確立に向けた、細胞膜の主要構成分子である細胞膜活性脂質 sphingolipidの新規機能に着目した基礎的研究である。がん死の首座を占める肺癌の進展制御のための基礎データの集積が本研究の社会的意義である。