title: Plexin-B1 and semaphorin 4D cooperate to promote cutaneous squamous cell carcinoma cell proliferation, migration and invasion.
abstract: OBJECTIVE
  Semaphorin 4D (Sema4D) and its receptor, Plexin-B1, are involved in the pathogenesis of squamous cell carcinoma (SCC) by mediating angiogenesis or perineural invasion through the interaction between Sema4D expression on SCC cells and Plexin-B1 expression on endothelial cells or nerves. Plexin-B1 was also recently found to be expressed on SCC cells. Plexin-B1 expression on several types of tumor cells could mediate various, and occasionally opposing, effects, including tumor cell survival, proliferation, angiogenesis, invasion, and metastasis. However, whether Sema4D exerts paracrine or autocrine effects on SCC via Plexin-B1 remains unclear.
  
  
  OBJECTIVE
  The aim of this study is to explore the effects of Sema4D/Plexin-B1 interaction on SCC via Plexin-B1 expressed on the tumor cells.
  
  
  METHODS
  In the present study, we detected the expression of Plexin-B1 and Sema4D in cutaneous SCC (cSCC) tissues and in the cSCC cell line A431 and analyzed the effects of the Sema4D/Plexin-B1 interaction on cSCC cell proliferation, migration, and invasion, as well as on the signaling pathway downstream of Plexin-B1.
  
  
  RESULTS
  We observed significantly increased Plexin-B1 and Sema4D expression in keratinocytes in cSCC lesions and in A431 cells compared with that in normal skin tissue and in non-malignant keratinocytes. Plexin-B1 silencing reduced the growth, proliferation, migration, and invasion of A431 cells and inhibited the phosphorylation of Akt and extracellular signal-regulated protein kinase (Erk). Soluble recombinant Sema4D promoted the growth, proliferation, migration, and invasion of A431 cells; Akt and Erk phosphorylation is also involved in these processes with a Plexin-B1 dependent manner.
  
  
  CONCLUSIONS
  Plexin-B1 induces cSCC cell proliferation, migration, and invasion by interacting with Sema4D. Plexin-B1 might serve as a useful biomarker and/or as a novel therapeutic target for cSCC.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Xianshui
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: fumeng@fmmu.edu.cn.
authors.forename: Meng
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: liwei1@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D015703:Antigens, CD / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004347:Drug Interactions; D006801:Humans; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D039961:Semaphorins / Q000494:pharmacology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C093224:CD100 antigen; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface; D039961:Semaphorins
keywords: Invasion; Migration; Plexin-B1; Semaphorin 4D; Squamous cell carcinoma