Does "humoral anticancer factor" secreted by normal epithelium cooperate with "cell competition" for cancer protection?

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K18302
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry; General anatomy (including histology/embryology)
• Research Institution: Tokyo Medical and Dental University (2022); Fukuoka Dental College (2017-2021)
• Principal Investigator: Kitagawa Norio 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40628517)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 細胞競合 / EDAC / Macropinocytosis / ケラチン５ / ケラチン１７ / 抗菌ペプチド / 癌 / ケラチノサイト

Outline of Final Research Achievements

Recent studies have shown that normal epithelial cells sense and actively eliminate neighboring cancer cells using physical forces without the help of immune cells. Although humoral anticancer factors seem to contribute to this elimination, there is a dearth of knowledge on the topic. Thus, we analyzed the effect of nisin, a humoral anticancer factor, on epithelial cells. Nisin treatment altered keratin (K)5 and K17 distribution in the cells, making them spherical, along with actin incorporation. Since the spherical distribution was >1 μm in diameter, the possibility of a macropinocytosis-like phenomenon was indicated. Nisin was effective under experimental conditions wherein micropinosome-like structures were not observed. Nisin administration induced derangement of the cell membrane, such as flip-flop, and disruption of the transmembrane structure of the keratins and desmosome protein.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

Macropinocytosisはアクチンとの関係が着目されることが多く、ケラチン（K）5、K17がMacropinocytosis様構造を包む報告は今までになく新規性がある。Macropinocytosisは癌細胞の代謝において重要な役割を果たすことが知られている。また、微小環境での癌細胞の生存に関係することから、癌の悪性度とも関連すると考えられており、微小環境でのMacropinocytosis様反応についてさらに解析していく必要性が示唆された。