机构：[1]Department of Oncology, The Affiliated Children’s Hospital of Kunming Medical University,[2]Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital,[3]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences,[4]Molecular Epidemiology Joint Laboratory, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College,[5]Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China昆明医科大学附属第一医院
Background: Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer. Materials and methods: The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis. Sema4D downregulation or overexpression was established by infection with lentiviruses-encoding Sema4D short hairpin RNA (shRNA) or Sema4D. To evaluate the effects of Sema4D on cell proliferation, cell cycle progression, apoptosis, invasion, and migration of MDA-MB-231 and MDA-MB-468 cells, methods including MTT assay, flow cytometry, wound healing assay, and transwell experiments were applied. BALB/c nude mice were injected with MDA-MB-231 cells, which were respectively infected with lentiviruses-encoding Sema4D, Sema4D shRNA, and GFP, followed by tumor angiogenesis assay. Results: Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines, especially in MDA-MB-231 and MDA-MB-468 cells. Cell proliferation ability was remarkably inhibited in Sema4D downregulated condition, whereas the proportions of cells in the G0/G1 phase and apoptosis increased in MDA-MB-231 and MDA-MB-468 cells. In addition, the invasion and migration abilities of these cells were obviously reduced. Xenograft growth as well as angiogenesis was inhibited when infected with lentiviruses-encoding Sema4D shRNA in vivo. Conclusion: Downregulation of Sema4D had notable influence on cell proliferation ability, invasion, migration, and apoptosis of both MDA-MB-231 and MDA-MB-468 cells. Furthermore, infection with lentiviruses-encoding Sema4D shRNA obviously inhibited tumor growth and angiogenesis in BALB/c nude mice. Our results showed that Sema4D may represent a novel therapeutic target for human breast cancer.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81171946]; Natural Science Foundation of Yunnan ProvinceNatural Science Foundation of Yunnan Province [2011CA016, 2012FB188]; Association Foundation Program of Yunnan Science and Technology Department and Kunming Medical University [2014FZ058]; Innovation Foundation of Kunming Medical University [2014D07]; Training Project for Medical Science and Technology Experts in Kunming City [SW-75]; Foundation of Yunnan Medical Science and Technology [2016NS124]
第一作者机构：[1]Department of Oncology, The Affiliated Children’s Hospital of Kunming Medical University,[2]Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital,
通讯作者：
通讯机构：[2]Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital,[*1]The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital, No 519 Kunzhou Road, Kunming, Yunnan Province 650106, People’s Republic of China
推荐引用方式(GB/T 7714)：
Jiang Hongchao,Chen Ceshi,Sun Qiangming,et al.The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer[J].ONCOTARGETS AND THERAPY.2016,9:5737-5750.doi:10.2147/OTT.S114708.
APA：
Jiang, Hongchao,Chen, Ceshi,Sun, Qiangming,Wu, Jing,Qiu, Lijuan...&Dong, Jian.(2016).The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.ONCOTARGETS AND THERAPY,9,
MLA：
Jiang, Hongchao,et al."The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer".ONCOTARGETS AND THERAPY 9.(2016):5737-5750
