Hyaluronan-TRP channel regulation in the induction of apoptosis in cancer spheroids

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06437
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nihon University
• Principal Investigator: YAMAZAKI Jun 日本大学, 生物資源科学部, 教授 (50230397)
• Co-Investigator(Kenkyū-buntansha): 岡村 和彦 福岡歯科大学, 口腔歯学部, 准教授 (00224056) ; 内田 邦敏 静岡県立大学, 食品栄養科学部, 准教授 (20581135)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: TRPチャネル / ヒアルロン酸 / がんスフェロイド / アポトーシス / 細胞浸潤

Outline of Final Research Achievements

Normal cells die when they are detached from the extracellular matrix. Hyaluronan (HA) is proposed to give cancer cells the resistance to the detachment-induced cell death. On the other hand, as HA is reported to inhibit the TRPV1 channel activity, it was supposed that HA regulates the TRPV1 channel activity during acquisition of malignancy in breast cancer. Therefore, we produced an in vitro model which mimics cancer spheroids invading into tissues. The results showed that addition of HA attenuates the TRPV1-mediated inhibition of cell migration and that endogenous HA constitutively suppresses the action of TRPV1. Interaction between TRPV1 and HA pathways could be a drug target to inhibit migration and invasion of cancer cells.

Free Research Field

イオンチャネル薬理学

Academic Significance and Societal Importance of the Research Achievements

がん細胞の遊走能や浸潤能を高める因子としてのヒアルロン酸（HA）やCa2+ 透過性を持つ TRP チャネルの役割が示唆されている中で、がん細胞塊からの遊走や浸潤におけるTRP チャネルとHA経路のクロストークを明らかにすることは新しい抗がんメカニズムを提示することに繋がる。がんスフェロイドの形成とそこからの規則的な細胞浸潤に焦点を当てた方法は、HAなどの細胞外基質を保持しながら細胞集団としての浸潤能を評価するモデルを提供するものと考えられる。