Development of novel therapeutic strategies for ovarian cancer by regulating the immunological dynamics of tumor-associated macrophages
| Project/Area Number |
19K09826
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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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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田代 浩徳 熊本大学, 大学院生命科学研究部(保), 教授 (70304996)
片渕 秀隆 熊本大学, 大学院生命科学研究部(医), 名誉教授 (90224451)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 卵巣癌 / 癌幹細胞 / 癌幹細胞ニッチ / マクロファージ / 腫瘍微小環境 / 腫瘍 |
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| Outline of Research at the Start |
難治性である卵巣癌の克服のためには、腹腔内播種病巣の腫瘍微小環境における抗癌剤治療抵抗性に関わる分子レベルでの病態の解明が必要不可欠であり、特に卵巣癌細胞と腫瘍随伴マクロファージとの細胞間相互作用、シグナル伝達に関わる分子機構を明らかにすることの重要性は論を俟たない。今回われわれは、これまでの解析で明らかにされた卵巣癌細胞とマクロファージとの関連性についての研究をさらに進展させることで、腫瘍微小環境の形成に関わるマクロファージの役割について、特に卵巣癌細胞との細胞間相互作用ならびに抗癌剤治療抵抗性に関与する分子メカニズムを解明する。
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| Outline of Final Research Achievements |
In this study, we performed a comprehensive basic analysis to elucidate the cell-cell interaction between ovarian cancer cells and TAMs and the molecular biological roles of CSF-1R and its ligand, CSF-1, in regulating TAM function.
We found that CSF-1 is expressed in ovarian cancer cells, while CSF-1R is expressed in TAMs. In addition, therapeutic experiments using CSF-1R inhibitors experimentally demonstrated that suppression of TAM function exerts an antitumor effect. These results suggest that suppression of these CSF-1/CSF-1R signaling pathways may be a promising new therapeutic strategy for ovarian cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
われわれの研究グループがこれまでに継続して行ってきたマクロファージの生物学的機能ならびに卵巣癌細胞の抗癌剤抵抗性に関する研究をさらに進展させ、特に腫瘍微小環境におけるTAMの機能的役割を明らかにすることは、卵巣癌の治療抵抗性の分子メカニズムの包括的な理解、そして卵巣癌患者の治療成績の向上に繋がることが期待される。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells2021
Author(s)
Artibani M, Masuda K, Hu Z, Rauher PC, Mallett G, Wietek N, Morotti M, Chong K, KaramiNejadRanjbar M, Zois CE, Dhar S, El-Sahhar S, Campo L, Blagden SP, Damato S, Pathiraja PN, Nicum S, Gleeson F, Laios A, Alsaadi A, Santana Gonzalez L, Motohara T, et al.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan2020
Author(s)
Onuki M, Matsumoto K, Iwata T, Yamamoto K, Aoki Y, Maenohara S, Tsuda N, Kamiura S, Takehara K, Horie K, Tasaka N, Yahata H, Takei Y, Aoki Y, Kato H, Motohara T, Nakamura K, Ishikawa M, Kato T, Yoshida H, Matsumura N, Nakai H, Shigeta S, Takahashi F, Noda K, Yaegashi N, Yoshikawa H.
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Journal Title
Cancer Sci
Volume: 117
Issue: 7
Pages: 2546-2557
DOI
Related Report
Peer Reviewed / Open Access
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