Roles of LPA receptors in the acquisition of malignant properties in cancer cells treated with anticancer drugs

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kindai University
• Principal Investigator: Tsujiuchi Toshifumi 近畿大学, 理工学部, 教授 (10254492)
• Co-Investigator(Kenkyū-buntansha): 朴木 寛弥 奈良県立医科大学, 医学部, 教授 (40336863)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: リゾフォスファチジン酸 / LPA受容体 / がん細胞 / 抗がん剤 / 抗がん剤抵抗性

Outline of Final Research Achievements

Lysophosphatidic acid (LPA) is a simple lipid and mediates various biological responses through the binding of G protein-coupled LPA receptors. Six subtypes of LPA receptors (LPA1) to LPA6) have been identified so far. It is considered that LPA receptor signaling is involved in the pathogenesis of human diseases, including cancer. In this study, we investigated the roles of LPA receptor signaling in the cellular functions induced by anticancer drug treatment in cancer cells. Our results have shown that the individual LPA receptors regulate cell motility, invasion and metastasis in cancer cells treated with anticancer drugs. Moreover, the activation of LPA receptor-mediated signaling promotes the modulation of anticancer drug resistance in cancer cells. Therefore, it is suggested that LPA receptor signaling is a potent pharmacological target for the establishment of effective chemotherapeutic agents.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究により、抗がん剤処理によって生じる様々ながん細胞の生物学的特性の変化にLPA受容体シグナルが促進または抑制的に作用することが明らかとなった。特に、抗がん剤に対する細胞生存率の制御にLPA受容体シグナルが関与することは、がん薬物療法を困難とさせる抗がん剤抵抗性を獲得したがん症例に対する効果的ながん薬物療法開発のための有用な情報源である。広範囲な浸潤や遠隔臓器への転移をきたした症例に対して、がん薬物療法は限られた選択肢のひとつであり、本研究を基盤とする新規分子標的療法の開発はこれからのがん治療成績向上にむけて大きな可能性のひとつを示したものである。