2023 Fiscal Year Final Research Report

Analysis of Brain metastasis mechanisms in small gell lung cancer for the identification of novel therapeutic targets

Research Project

PDF

Project/Area Number	21K06957
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 49030:Experimental pathology-related
Research Institution	Microbial Chemistry Research Foundation
Principal Investigator	Sakamoto Shuichi 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 主任研究員 (60346070)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	小細胞肺がん / がん転移
Outline of Final Research Achievements	To identify factors involved in the formation of brain metastases in small cell lung cancer, we repeatedly transplanted the human small cell lung cancer cell line DMS273 into the brain parenchyma of nude mice, generating two cell lines with enhanced tumorigenic potential in the brain. Additionally, for comparative purposes, we transplanted the cells into the subcutaneous tissue of nude mice, creating two cell lines with enhanced tumorigenic potential in the subcutaneous tissue. Analysis of the gene expression profiles of these cells revealed an increased expression of gene X, which encodes a lipid transporter, in the cells that had undergone repeated brain transplantation. Knockdown of gene X in these cells resulted in a significant decrease in sphere-forming ability in vitro and a trend toward reduced tumorigenic potential in nude mice.
Free Research Field	腫瘍生物学
Academic Significance and Societal Importance of the Research Achievements	本研究でヒト小細胞肺がん細胞株DMS273をヌードマウス脳実質あるいは皮下での腫瘍形成を繰り返して作成した細胞群は、表現型や遺伝子発現プロファイルにそれぞれ特徴がある。これは脳実質あるいは皮下の微小環境への適応機構の違いを反映している可能性があり、その解析における有用な研究材料となるだろう。実際に、それらの細胞群の解析から着目した遺伝子Xは、これまで小細胞肺がんにおける意義は不明だったが、小細胞肺がん細胞株のスフェア形成能や腫瘍形成能への寄与が示唆された。今後のさらなる解析により、遺伝子Xは有効な治療法が少ない小細胞肺がんの新たな治療標的となる可能性がある。