骨髓基质细胞通过TSP-1/CD36通路对急性髓系白血病细胞影响的初步研究  

Bone marrow-derived mesenchymal stromal cells affected acute myeloid leukemia cells via the TSP-1/CD36 pathway

作　　者：郑雅心 亢俊楠 陈泽慧 王丽娜 郑国光 热西担·努尔买买提 田晨 Yaxin Zheng;Junnan Kang;Zehui Chen;Lina Wang;Guoguang Zheng;Nuermaimaiti Rexidan;Chen Tian(Department of Hematologic Oncology,Tianjin Medical University Cancer Institute&Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China;Hotan District People's Hospital,Hotan 848000,China;Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Med-ical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]天津医科大学肿瘤医院血液科,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市“肿瘤防治”重点实验室,天津市300060 [2]新疆和田地区人民医院 [3]中国医学科学院血液病医院(血液学研究所)

出　　处：《中国肿瘤临床》2023年第4期167-171,共5页Chinese Journal of Clinical Oncology

基　　金：新疆维吾尔自治区自然科学基金面上项目(编号:2022D01A09);天津市卫生健康科技项目(编号:ZC20171);天津市医学重点学科(专科)建设项目(编号:TJYXZDXK-009A)资助。

摘　　要：目的:探讨骨髓基质细胞(bone marrow-derived mesenchymal stromal cells,BM-MSCs)对急性髓系白血病(acute myeloid leukemia,AML)细胞影响的作用机制。方法:构建MLL-AF9过表达诱导的AML小鼠模型,通过PCR比较AML小鼠和野生型小鼠(WT)BM-MSCs内TSP-1的表达差异。通过慢病毒载体使AML小鼠来源的BM-MSCs高表达TSP-1后,与AML细胞行transwell共培养,检测AML细胞表面TSP-1受体CD36及CD47的表达及AML细胞的生长情况。在共培养体系中加入CD36抑制剂N-油酰基硫代琥珀酰亚胺,检测AML细胞增殖、凋亡的变化。结果:AML小鼠BM-MSCs中TSP-1的表达低于对照组。过表达TSP-1的BM-MSCs与AML细胞行transwell共培养后AML细胞的生长受到抑制,且AML细胞表面的CD36受体表达升高,但CD47表达无明显差异。在共培养体系中加入CD36抑制剂N-油酰基硫代琥珀酰亚胺后,AML细胞增殖加快,凋亡减少。结论:TSP-1/CD36信号通路有望成为治疗AML的潜在靶点。Objective:To investigate the mechanism of impact of bone marrow-derived mesenchymal stromal cells(BM-MSCs)on acute myeloid leukemia(AML)cells.Methods:An overexpressed MLL-AF9-induced AML mouse model was used,and the expression of thrombospondin-1(TSP-1)was compared between BM-MSCs from AML and wild-type(WT)mice by PCR analysis.TSP-1-overexpressing BM-MSCs were co-cultured with primary AML cells following lentivirus transfection,and the growth of AML cells and expression of TSP-1 receptors(CD36 and CD47)on their surface was detected.The CD36 inhibitor N-oleoylthiosuccinimide was introduced to the co-culture system and AML cell proliferation and apoptosis were observed.Results:TSP-1 expression in BM-MSCs derived from AML mice was lower than that in WT mice.Flow cytometry results revealed that CD36 expression increased but CD47 expression remained unchanged in primary AML cells cocultured with TSP-1-overexpressing BM-MSCs.Furthermore,AML cell growth was inhibited following co-culturing with TSP-1-overexpressing BM-MSCs.The addition of N-oleoylthiosuccinimide increased AML cell proliferation while inhibiting apoptosis.Conclusions:TSP-1/CD36 signaling could be a potential therapeutic target for AML.

关 键 词：骨髓基质细胞 急性髓系白血病 TSP-1 CD36 

分 类 号：R733.71[医药卫生—肿瘤]