title: The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, The Affiliated Children's Hospital of Kunming Medical University; Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Molecular Epidemiology Joint Laboratory, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College.
authors.forename: Qiangming
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Molecular Epidemiology Joint Laboratory, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Change
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital.
authors.forename: Nie
authors.initials: N
authors.lastname: Jun
authors.affiliation: Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital.
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
keywords: angiogenesis; apoptosis; breast cancer; proliferation; semaphorin 4D