2022 Fiscal Year Final Research Report
Targeting therapy of C5a receptor on cancer associated fibroblast control pancreatic cancer stemness
| Project/Area Number |
20K09081
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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 55020:Digestive surgery-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
今井 克憲 熊本大学, 大学院生命科学研究部(医), 特定研究員 (60555746)
林 洋光 熊本大学, 病院, 講師 (80625773)
山村 謙介 熊本大学, 大学院生命科学研究部(医), 特定研究員 (10816507)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | C5a receptor / C5a / Pancreatic cancer / CAFs / cancer stemness |
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| Outline of Final Research Achievements |
Targeting C5a-C5aR therapeutically in pancreatic cancer may control cancer stem cells and lead to new pancreatic cancer treatments. In addition, targeting C5aR expressed on cancer-associated fibroblasts (CAFs) may lead to new targeting therapy for pancreatic cancer.
From the results of our research, we revealed that C5aR-positive CAFs are activated by C5a, and that co-culturing C5a-stimulated CAFs and pancreatic cancer cells enhances the invasion ability of cancer cells. From the above, it was suggested that blocking C5aR expressed in CAFs suppresses the progression of pancreatic cancer cells, so C5aR may become a new target in pancreatic cancer in the future. However, we examined the sphere-forming ability of C5a and pancreatic cancer stem cells, but could not demonstrate the relationship between C5a and cancer stem cells.
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| Free Research Field |
Cancer cell biology
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| Academic Significance and Societal Importance of the Research Achievements |
難治性癌の代表格である膵癌は腫瘍の増大に間質増生を伴うことが特徴的である。特に膵癌間質細胞の大部分をしめるCAFsは膵癌の浸潤、制癌剤耐性に重要な働きを示している。今回の研究結果からCAFsはC5aRを発現しており、これがC5aによって刺激されることが明らかとなった。さらにC5aで刺激されたCAFsは膵癌細胞の浸潤能を高めることが分かった。以上より膵癌においてC5aRをターゲットとした治療が有効であることが示唆されたため、膵癌の新たな治療として期待できる。
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