Research of the mechanism of bone resorption by the cancer: Comprehensive analysis focusing on the regulation of RANKL expression and osteoclastogenesis.
Project/Area Number |
19K10266
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 57060:Surgical dentistry-related
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Research Institution | Hiroshima University (2021-2022) Osaka University (2019-2020) |
Principal Investigator |
Aikawa Tomonao 広島大学, 医系科学研究科(歯), 教授 (00362674)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 骨吸収 / 扁平上皮癌 / IL-7 / RANKL / T細胞 / SCC / 破骨細胞 / RNAKL / 口腔がん / 骨浸潤 / 顎骨 / 腫瘍 |
Outline of Research at the Start |
本研究は、腫瘍細胞と間質線維芽細胞そして破骨細胞の相互作用に焦点をあて、口腔がんによりなぜ骨が破壊されるのか、骨を吸収・破壊する腫瘍としない腫瘍になぜ別れるのか、それはどのような機序で、どのようなタンパクが関わっているのか、を明らかにする研究である。わたしたちが作成した骨破壊型のマウスモデルと、骨破壊の少ないマウスモデルから遺伝子を抽出し、網羅的にどのような遺伝子が発現しているのかを調べる予定である。 本研究でがん細胞と周囲の正常細胞、がん細胞と周囲の破骨細胞の相互作用を明らかにし、普遍的な機序を解明することで、将来的ながんの骨破壊に関わる標的分子研究の基礎になればと考えている。
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Outline of Final Research Achievements |
The molecular mechanisms of bone resorption and destruction in squamous cell carcinoma were analyzed using a syngeneic mouse model of cranial bone invasion. Squamous cell carcinoma cell line cells; SCC7-derived high- and low-resorption sub cell line cells were used to analyze gene expression in bone-resorbing and non-bone-resorbing areas by RNA sequencing. We found that interleukin 7 (IL- 7) was the highly expressed soluble factors in the high bone-resorption area. Administration of anti-LI-7 neutralizing antibody to the high bone resorption subline tumors markedly reduced RANKL gene expression, TRAP gene expression, and cathepsin K gene expression in the tumors, and also markedly suppressed bone resorption. The results suggest that IL-7 would be involved in bone resorption by squamous cell carcinoma cells.
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Academic Significance and Societal Importance of the Research Achievements |
多くの癌腫の治療法の確立と治療の向上により、原発巣病変の治癒が向上している。しかしながら、他臓器転移病巣、例えば骨転移などの骨病変に対する治療は困難を極める。口腔扁平上皮癌においては、骨病変の成立機序も明らかにされておらず、治療手法が少ないのが現状である。 本研究は骨浸潤の分子機序を明らかにするという学術的な意義に加え、将来的な口腔扁平上皮癌の骨病変治療の基礎となりうる点で医療的な、社会的な意義も大きい。
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] Sunitinib promotes apoptosis via p38 MAPK activation and STAT3 downregulation in oral keratinocytes.2022
Author(s)
Fukada S, Ohta K, Sakuma M, Akagi M, Kato H, Naruse T, Nakagawa T, Shigeishi H, Nishi H, Takechi M, Aikawa T.
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Journal Title
Oral Disease
Volume: in press
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of angiogenesis and tumor progression of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma.2022
Author(s)
Nakagawa T, Ohta K, Naruse T, Sakuma M, Fukada S, Yamakado N, Akagi M, Sasaki K, Niwata C, Ono S, Aikawa T.
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Journal Title
J Cancer Res Clin Oncol.
Volume: 148
Issue: 12
Pages: 3281-3292
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of CEACAM1 in oral keratinocytes on HO-1 expression induced by Candida β-glucan particles.2022
Author(s)
Sakuma M, Ohta K, Fukada S, Akagi M, Kato H, Ishida Y, Naruse T, Takechi M, Shigeishi H, Nishi H, Aikawa T.
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Journal Title
J Appl Oral Sci.
Volume: 30
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tumor budding and adjacent tissue at the invasive front correlate with delayed neck metastasis in clinical early-stage tongue squamous cell carcinoma.2019
Author(s)
Yamakawa N, Kirita T, Umeda M, Yanamoto S, Ota Y, Otsuru M, Okura M, Kurita H, Yamada SI, Hasegawa T, Aikawa T, Komori T, Ueda M; Japan Oral Oncology Group (JOOG)
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Journal Title
J Surg Oncol
Volume: 119
Issue: 3
Pages: 370-378
DOI
Related Report
Peer Reviewed / Open Access
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