Cancer cell interaction mechanisms caused by the complexity of breast cancer tissues

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Keio University
• Principal Investigator: Arima Yoshimi 慶應義塾大学, 医学部(信濃町), 専任講師 (20309751)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 乳がん

Outline of Final Research Achievements

Cancer is genomically and phenotypically diverse and composed of complex tissues, including tumor microenvironments and a heterogeneous population of cancer cells, all showing different characteristics. We formed heterogeneous cancer tissues by mixing two different human-derived triple-negative breast cancer cell lines and inoculating them into the mammary fat pads of immunodeficient mice. These heterogeneous cancers were more proliferative than the homogeneous cancers that were formed by individually inoculating the cell lines. We performed RNA-sequencing analysis to identify the genes which characteristically expressed in heterogeneous cancer tissues. Our hallmark genes seem to be involved in tumor growth and could be important biomarkers of intratumoral heterogeneity associated with malignancy and therapeutic resistance of breast cancers.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がんはゲノム的にも形質的にも多様であり、異なる性質を持つ不均一ながん細胞の集団と、その微小環境で構成される複雑な組織であることが知られている。腫瘍内不均一性は、がんのさらなる悪性化を誘導し、治療を困難にする原因となるため、がんの不均一性を標的とした治療法の開発を目指して本研究を行っている。がん組織内の不均一性がどのような機序で、乳がんの悪性度または治療抵抗性に関与するか解明できれば、今後の乳がん治療に大きく貢献できると考えられる。本研究によって見出した因子は、乳がんの悪性度および治療抵抗性と関連する腫瘍内不均一性のバイオマーカーとなる可能性が考えられた。