Establishing a 3D model of fibrosis in pancreatic cancer and analysis of interaction between tumor cells and stellate cells
| Project/Area Number |
18H02797
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Okayama University |
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Principal Investigator |
Kano Mitsunobu 岡山大学, ヘルスシステム統合科学学域, 教授 (80447383)
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| Co-Investigator(Kenkyū-buntansha) |
正宗 淳 東北大学, 医学系研究科, 教授 (90312579)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| Keywords | 膵がん / 間質 / 線維化 / 三次元培養 / 三次元培養法 / 細胞外基質 / 線維芽細胞 / 腫瘍微小環境 / 薬物送達 / 膵星細胞 / 膵臓がん / 膵臓星状細胞 / 膵癌 / 膵臓星状細胞（PSC） / 立体培養 |
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| Outline of Final Research Achievements |
Our hypothesis is that fibrosis within tumour tissue is an important determinant of clinical drug efficacy. We worked on the verification of this hypothesis through three-dimensional culture of its constituent cells, pancreatic stellate cells (PSCs). Specifically, the thickness of fibrotic tissue was measured in human cases and three-dimensional cultured tissue with equivalent thickness was created. The ECM proteins involved in fibrosis were visualised and analysed in the fibrotic tissue model, and differences between pancreatic cancer-derived PSCs and normal fibroblasts were revealed. We developed a three-dimensional co-culture model between PSCs and pancreatic cancer cells, and succeeded in creating three-dimensional co-cultured tissue that reproduced the range of tumour tissue occupancy rates observed clinically. Consequently, we were able to reproduce and analyse mechanism of the acquisition of PSC trait abnormalities by co-culturing with pancreatic cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
膵がんは我が国のがん死亡の原因4位である。特にその8割以上を占める膵管腺癌は難治である。膵がんの五年生存率は依然として1割前後であり、数十年来、本質的な改善がない。特に手術適応のない進行性膵がんでは、抗腫瘍剤が主な治療法であるが不応例が多い。膵がんで薬物療法の奏功程度が低い原因は、腫瘍細胞そのものの薬剤感受性や抵抗性を含めて様々ありうるなか、本研究では顕著な腫瘍組織内の線維化が臨床薬効の重要な規定因子であるという仮説の検証を進めた。膵がんを含む線維化を伴う疾患の新規治療法開拓への礎となることが期待される。
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Report
(5 results)
Research Products
(29 results)
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[Journal Article] In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers2019
Author(s)
Watanabe S, Hayashi K, Toh K, Kim HJ, Liu X, Chaya H, Fukushima S, Katsushima K, Kondo Y, Uchida S, Ogura S, Nomoto T, Takemoto H, Cabral H, Kinoh H, Tanaka HY, Kano MR, Matsumoto Y, Fukuhara H, Uchida S, Nangaku M, Osada K, Nishiyama N, Miyata K, Kataoka K
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Journal Title
Nature Communications
Volume: 10
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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