Elucidation of the role of the increase of interstitial pressure on the pathophysiology of lung cancer and the development of novel treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15513
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tokuda Shinsaku 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00433277)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肺癌 / 間質圧 / 細胞極性 / 腫瘍微小環境 / 細胞運動

Outline of Final Research Achievements

The role of increased interstitial pressure on cancer cells is unknown. We investigated the effects of hydrostatic pressure on lung cancer cells. The pressure from basal side promoted cell proliferation, induced abnormal cell polarity, accelerated cell migration, and induced stratification of the epithelia. These results revealed that the increased interstitial pressure contributes tumor progression and plays an important role in the pathophysiology of lung cancer.
In addition, we investigated the mechanism by which lung cancer cells sense the pressure from basal side. The pressure from basal side is thought to generate the mechanical force to tight junctions. Therefore, we established knockout cell clones of ZO-1, one of the major tight junction proteins. However, ZO-1 knockout cell clones did not form epithelial sheet and we could not test the effect of pressure from basal side experimentally. We developed the method to study the effect of pressure to overcome this technical problem.

Free Research Field

がん細胞生物学

Academic Significance and Societal Importance of the Research Achievements

進行期の肺癌に対する治療は近年進歩しており、細胞障害性抗がん剤に加えて分子標的薬や免疫治療の開発が進み、治療成績も向上している。しかし、未だに進行期の肺癌は根治が難しい状況である。腫瘍の周囲では物理的な圧力が高くなっているが、本研究では物理的な圧力が肺癌の促進に重要な役割を果たしていることを明らかにした。今後、癌細胞が圧力を感知するメカニズムの詳細がさらに明らかになれば、肺癌の新たな治療法の開拓につながることが期待される。