Investigate and control of new lymph node metastasis mechanism CCID formation in pancreatic cancer
| Project/Area Number |
16K10602
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
YASUI Takaharu 九州大学, 医学研究院, 共同研究員 (60611283)
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| Co-Investigator(Kenkyū-buntansha) |
寅田 信博 九州大学, 大学病院, 臨床検査技師 (00398075)
森山 大樹 九州大学, 大学病院, 准教授 (70586859)
大内田 研宙 九州大学, 大学病院, 講師 (20452708)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 膵癌 / リンパ節転移 / CCID formation / Collective invasion / CCIDformation / 微小リンパ節転移 / リンパ管内皮細胞 |
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| Outline of Final Research Achievements |
Time-lapse microscopic imaging revealed that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. The addition of supernatant from the cultured cancer cells enhanced CCID formation. Microarray analysis revealed that the expression of S100P was significantly increased when Lymphatic endothelial cells (LECs) were treated with the supernatant of cultured cancer cells. S100P expression in LECs increased after the addition of IL-6. IL-6 treatment increased migration in LECs and CCID formation. The extracellular S100P increased migration in LECs and CCID formation. The antagonist of S100P significantly suppressed the migration of LECs and CCID formation in LECs. The present findings demonstrated that CCIDs in pancreatic cancer are partly regulated by S100P, suggesting that S100P is a promising target to inhibit lymph node metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌は予後不良の疾患であり、早期診断・治療が困難で、発見時にすでに高度浸潤、遠隔転移を伴うことが多い。その中で、リンパ節転移は高頻度に見られ予後を左右すると言われているが、その機序は不確かな部分が多い。本研究では、膵癌におけるCircular chemorepellent-induced defects (CCID) formationがS100Pによって部分的に調節されており、リンパ節転移を阻害するための有望な標的であることが示唆された。この結果が次世代の個別化治療の開発につながれば、学術的にも広範な波及効果が期待され、将来の膵癌患者の予後改善に貢献をもたらす可能性があると思われる。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Degree of desmoplasia in metastatic lymph node lesions is associated with lesion size and poor prognosis in pancreatic cancer patients2017
Author(s)
Nakayama H, Ohuchida K, Yoshida M, Miyazaki T, Takesue S, Abe T, Endo S, Koikawa K, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Shirahane K, Manabe T, Ohtsuka T, Toma H, Tominaga Y, Nagai E, Mizumoto K, Oda Y, Nakamura M.
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Journal Title
Oncology Letters
Volume: 14
Issue: 3
Pages: 3141-3147
DOI
Related Report
Peer Reviewed
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[Journal Article] Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination.2017
Author(s)
Abe T, Ohuchida K, Koikawa K, Endo S, Okumura T, Sada M, Horioka K, Zheng B, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
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Journal Title
Int J Oncol
Volume: 50
Issue: 2
Pages: 457-467
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] A novel mechanism in lymphatic metastasis of pancreatic cancer2017
Author(s)
Nakayama H, Ohuchida K, Takesue S, Kibe S, Ando Y, Abe T, Endo S, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Shirahane K, Tominaga Y, Ohtsuka T, Mizumoto K, Nakamura M
Organizer
The 48th Annual Meeting of The American Pancreatic Association
Related Report
Int'l Joint Research
