Exosomes derived from colorectal cancer are associated with niche formations.

Research Project

Project/Area Number	18K15803
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Tohoku University
Principal Investigator	Kuroha Masatake 東北大学, 大学病院, 助教 (70709469)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	大腸癌幹細胞 / エクソソーム / 大腸癌
Outline of Final Research Achievements	Exosomes are membrane-enclosed nanovesicles and have been increasingly recognized as important cell communications by transmitting microRNA (miRNA).Development of a three-dimensional organoid culture system allows us to perform long-term expansion of epithelial organoids of human CRA and CRC. We established six CRC patient-derived organoids and eight CRA patient-derived organoids. We analyzed the exosomal and cellular microRNA expression profiles by miRNA microarray. We found different miRNA expression profiles between CRC- and CRA-derived organoids, and that both exosomal and cellular miR-1246 expression was upregulated in CRC-derived organoids compared to CRA-derived organoids. Alteration of miR-1246 expression by miR-1246 mimic or inhibitor accordingly increased or decreased cell proliferation in HT-29 CRC cell line, respectively. In conclusion, we here reported upregulation of miR-1246 might play a role in increased cell proliferation in colorectal adenoma-carcinoma transition.
Academic Significance and Societal Importance of the Research Achievements	３次元オルガノイド培養システムからエクソソームを抽出した。オルガノイド培養上清から抽出可能という知見は新規である。また、腫瘍の進行度によりエクソソームの性質が異なることを明らかとした。されにはニッチ形成に関与していることも明らかとした。大腸癌が発育にともない、癌は周囲の細胞、もしくは自身のheterogeneityに適応するために分泌している可能性が推定され、大腸癌の発育進展の機序解明に重要な知見がえられた。