Elucidation of complex microenvironmental crosstalk between pancreatic cancer progression and obesity
| Project/Area Number |
19K17407
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Nishigaki Ruriko 名古屋市立大学, 医薬学総合研究院(医学), 臨床研究医 (60835164)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 膵癌 / 肥満 / 脂肪細胞 / 内臓脂肪 |
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| Outline of Research at the Start |
非肥満マウス・肥満マウスのそれぞれの内臓脂肪組織から、脂肪前駆細胞を初代培養し、①膵癌細胞の単培養をコントロールとし、膵癌細胞と②非肥満内臓脂肪細胞、③肥満内臓脂肪細胞、の共培養を行い肥満脂肪細胞が膵癌細胞にもたらす影響を検討する。さらに、血管内皮細胞との共培養も行い、膵癌細胞・脂肪細胞が血管新生にもたらす影響を検討する。それぞれの現象のメカニズムを分子生物学的に解明した後、動物実験やヒト膵癌組織を使用し検証する。
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| Outline of Final Research Achievements |
Visceral adipocytes cell lines were established from lean (L-Adv) and obese mice (O-Adv). Conditioned media from O-Adv significantly increased PDAC cell growth and migration and angiogenic capacity in both human and mice cells,compared to conditioned media from L-Adv. Blocking osteopontin (OPN) in O-Adv canceled O-Adv-induced effects through suppressing AKT phosphorylation and VEGFA expression.In the xenograft model, PDAC tumor volume was significantly increased in obese mice compared with lean mice, whereas blocking OPN significantly inhibited obesity-accelerated tumor growth. In PDAC patients with obesity, high OPN expression in adipose tissues was significantly associated with poor prognosis. In conclusion, obese adipocytes trigger aggressive transformation in PDAC cells to induce PDAC progression and accelerate angiogenesis via OPN secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
過去の複数の疫学的研究により、肥満は膵癌のリスク因子であること、予後不良因子であることがわかっているが、そのメカニズムは不明である。本研究では、細胞実験・動物実験・ヒトの膵癌組織を使用し多角的に検討をおこない、肥満患者の脂肪細胞ではオステオポンチンが高発現し、血管新生を促進し膵癌細胞を悪性化へと誘導するという新たな知見をえた。今後の肥満関連の治療開発や膵癌予防への発展が期待される。
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Report
(3 results)
Research Products
(6 results)
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[Journal Article] Urinary microRNA biomarkers for detecting the presence of esophageal cancer.2021
Author(s)
Okuda Y, Shimura T, Iwasaki H, Fukusada S, Nishigaki R, Kitagawa M, Katano T, Okamoto Y, Yamada T, Horike SI, Kataoka H.
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Journal Title
Sci Rep.
Volume: 11
Issue: 1
Pages: 8508-8508
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Relationship between Immunophenotype and Clinicopathological Findings for Superficial Nonampullary Duodenal Epithelial Tumor2021
Author(s)
Fukusada S, Shimura T, Iwasaki H, Okuda Y, Katano T, Nishigaki R, Ozeki T, Kitagawa M, Nishie H, Tanaka M, Ozeki K, Kubota E, Tanida S, Kataoka H
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Journal Title
Digestion
Volume: Apr 1
Issue: 6
Pages: 1-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma2020
Author(s)
Okuda Y, Shimura T, Iwasaki H, Katano T, Kitagawa M, Nishigaki R, Fukusada S, Natsume M, Tanaka M, Nishie H, Ozeki K, Yamada T, Kataoka H.
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Journal Title
Digestion.
Volume: Oct 13
Issue: 4
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access
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