Cell fusion connects fusion gene generation with tumor evolution

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15262
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TAJIMA Youichi 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (00300955)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞融合 / 融合遺伝子 / 間葉系幹細胞

Outline of Final Research Achievements

Cell fusion likely drives tumor evolution by undermining chromosomal and DNA stability and by generating phenotypic diversity. However, whether a cell fusion event can initiate malignancy tumor evolution is unknown. We report that a fusion event between mesenchymal stem cells (MSCs) and bladder cancer cell line (UMUC-3) can initiate generation of fusion genes, cell transformation, and malignancy. We also reported that cell fusion induced the expression of genes including the X-gene associated with an aggressive phenotype. Hybrids depleted the X-gene suppressed tumor formations. These results suggested cell fusion event between MSCs and cancer cells is involve in tumor evolution by generation phenotypic diversity.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がんの増悪化に細胞融合が関与する可能性は100年前から指摘されていたが、明確に証明した研究は殆どない。我々は細胞融合により新たに融合遺伝子が形成される可能性を検討した。がんの増悪化に細胞融合が一端を担っていれば、細胞融合に特化した創薬開発に繋がる可能性が考えられる。