Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer
Project/Area Number |
16K15607
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Chiba University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
佐藤 守 千葉大学, 医学部附属病院, 特任准教授 (20401002)
吉富 秀幸 千葉大学, 大学院医学研究院, 准教授 (60375631)
宮崎 勝 国際医療福祉大学, 大学病院, 教授 (70166156)
酒井 望 千葉大学, 医学部附属病院, 助教 (70436385)
賀川 真吾 千葉大学, 医学部附属病院, 助教 (90507302)
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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 |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 膵癌 / Annexin II / Tenascin C / 癌細胞ー間質相互作用 / 浸潤 / 転移 / 膵臓外科学 / 浸潤・転移 / 癌 |
Outline of Final Research Achievements |
The interaction of cancer cells and stromal components contributes to cancer progression. We explored the correlation of annexin II (ANX2) and stromal tenascin C (TNC) with pancreatic cancer (PDAC) progression. In ANX2 knockdown cells, there were fewer cells with a mesenchymal appearance in 3D culture and reduced invasion. Morphological change into mesenchymal phenotype and invasion were enhanced more by recombinant TNC treatment in control cells but not in ANX2 knockdown cells. Pancreatosphere formation assays showed that both ANX2 and TNC facilitated stem-like characters, and anoikis assays indicated that the ANX2-TNC interaction contributes to anoikis resistance in PDAC cells. In IHC analyses, the ANX2 High/stromal TNC High expression group showed a significant correlation with distant metastasis and poor outcomes after surgery. In conclusion, ANX2 and stromal TNC regulate invasion along with stemness and anoikis resistance, which are crucial for metastasis in PDAC progression.
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Academic Significance and Societal Importance of the Research Achievements |
膵癌は最も予後不良な癌であり、5年生存率は未だ10%に満たない疾患である。その最大の理由の1つとして挙げられるのは、膵癌自体の悪性度の高さ(浸潤・転移能)と考えられる。本研究でAnnexin-IIとTenascin Cによる、癌細胞と癌周囲微小環境の相互作用について明らかとなったことで、膵癌進展機序の解明および今後の新規治療開発につながる研究成果と考えられる。本研究の内容については2018年 International Journal of Molecular Medicineに受理され、論文報告された。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer.2018
Author(s)
Yoneura N, Takano S, Yoshitomi H, Nakata Y, Shimazaki R, Kagawa S, Furukawa K, Takayashiki T, Kuboki S, Miyazaki M, Ohtsuka M.
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Journal Title
Int J Mol Med.
Volume: 42
Pages: 821-830
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Conversion surgery with gemcitabine plus nab-paclitaxel for locally advanced unresectable pancreatic cancer: A case report.2018
Author(s)
Okura R, Takano S, Yokota T, Yoshitomi H, Kagawa S, Furukawa K, Takayashiki T, Kuboki S, Suzuki D, Sakai N, Nojima H, Mishima T, Miyazaki M, Ohtsuka M.
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Journal Title
Mol Clin Oncol.
Volume: 9
Pages: 389-393
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Annexin II and stromal tenascin C expression promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer2018
Author(s)
Naoko Yoneura, Shigetsugu Takano*, Hideyuki Yoshitomi, Yasuyuki Nakata, Reiri Shimazaki, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
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Journal Title
International Journal of Molecular Medicine
Volume: 印刷中
Related Report
Peer Reviewed / Open Access
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[Journal Article] Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer.2017
Author(s)
Satoh M, Takano S, Sogawa K, Noda K, Yoshitomi H, Ishibashi M, Mogushi K, Takizawa H, Otsuka M, Shimizu H, Miyazaki M, Nomura F.
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Journal Title
Cancer Sci.
Volume: 印刷中
Issue: 4
Pages: 795-803
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags.2016
Author(s)
Sogawa K, Takano S, Iida F, Satoh M, Tsuchida S, Kawashima Y, Yoshitomi H, Sanda A, Kodera Y, Takizawa H, Mikata R, Ohtsuka M, Shimizu H, Miyazaki M, Yokosuka O, Nomura F.
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Journal Title
Br J Cancer.
Volume: 115
Issue: 8
Pages: 949-956
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] ETS-Transcription Factor ETV1 Regulates Stromal Expansion and Metastasis in Pancreatic Cancer.2016
Author(s)
Heeg S, Das KK, Reichert M, Bakir B, Takano S, Caspers J, Aiello NM, Wu K, Neesse A, Maitra A, Iacobuzio-Donahue CA, Hicks P, Rustgi AK.
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Journal Title
Gastroenterology.
Volume: 151
Issue: 3
Pages: 540-553
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Prrx1 isoform switching regulates pancreatic cancer invasion and metastatic colonization2016
Author(s)
Shigetsugu Takano, Maximilian Reichert, Basil Bakir, Koushik K. Das, Takahiro Nishida, Masaru Miyazaki, Steffen Heeg, Meredith A. Collins, Benoît Marchand, Philip D. Hicks, Anirban Maitra, and Anil K. Rustgi
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Journal Title
GENES & DEVELOPMENT
Volume: 30
Issue: 2
Pages: 233-247
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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