大腸癌細胞と骨髄に由来するFibrocyteの相互作用に関する研究

结直肠癌细胞与骨髓来源纤维细胞相互作用的研究

• 批准号: 22K15961
• 负责人: 寺井 志郎
• 金额: $ 1.83万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K15961/
• 关键词: fibrocyte; がん微小環境; 線維化

本研究では、大腸癌細胞が産生・放出するTGF-β、PDGFやFGFといった線維化を促進させる種々の増殖因子、ケモカインにより血中を循環するFibrocyteが癌組織内に遊走され、癌間質内でCAFsへと分化し、癌細胞の増殖や上皮間葉転換（EMT）に寄与することを明らかにするため以下の検討を進めていく。本年度は手術により採取された大腸癌切除標本を用いて、E-cadherin、Vimentin、αSMAなどのEMTに関するマーカーの発現やSDF-1α、MCP-1、CXCR4、CCLなどのFibrocyteを誘導するケモカインおよびその受容体の発現を免疫組織染色にて解析した。大腸癌原発巣の間質内において、αSMA、VimentinなどのEMTマーカーやFibrocyteに対する走化因子であるSDF-1α、CCL2およびその受容体であるCXCR4などの発現が確認された。今後は蛍光免疫染色にてCXCR4を発現する細胞のうちFibrocyteマーカーであるCD34の2重染色でCXCR4発現陽性細胞中のFibrocyteの割合を検討する。また健常人の末梢血単核球より分離培養したFibrocyteを各種大腸癌細胞株(CACO-2、HCT116、CW-2)と関節共培養を行い、大腸癌細胞株のEMTマーカーやFibrocyteに対する各種ケモカイン(SDF-1α、MCP-1、CCL2)の発現をまたFibrocyteのEMT マーカーやCXCR4の発現をwestern blotおよびELSIAにて解析中である。

In this study, TGF- β was released from the tumor cells of large cancer cells, TGF- β was released from the cells of large cancer cells, and PDGF was used to promote the proliferation of several tumor factors. In this study, the tumor cells of large cancer cells released TGF- β, the cells of large cancer cells released Fibrocyte β, the cells of large cancer cells promoted the growth of several tumor growth factors, and the serum samples of cancer cells were detected by Fibrocyte in the same way. CAFs differentiation in cancer cells, cancer cell colonization and epithelial cell culture (EMT) were confirmed by Elisa and Elisa. In this year's surgical procedure, the major cancer resection labels were identified by using SDF-1 α, E-cadherin, Vimentin, α SMA, EMT, CXCR4, CCL, MCP-1, MCP-1, CXCR4, and CCL to detect immune tissue staining and immunoassay. The carcinogens of Dazhou were infected with SDF-1, α SMA, Vimentin, EMT, Fibrocyte, Fibrocyte, SDF-1 α, CCL2, capacitor, CXCR4, and confirmation. After light immunostaining, CXCR4 showed that the cells were divided into Fibrocyte cells, Fibrocyte cells, CD34 cells, CXCR4 cells, sexual cells, Fibrocyte cells. All kinds of large cancer cell lines (CACO-2, HCT116, CW-2) of healthy people were isolated and cultured together. The cell lines of large cancer (CACO-2, HCT116, CW-2) were cultured together, and the cancer cell lines of EMT, Fibrocyte, and CCL2 (SDF-1 α, MCP-1, CCL2) were tested. The results showed that Fibrocyte EMT antibody CXCR4 was detected in the analysis.