title: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.
abstract: The semaphorins and plexins comprise a family of cysteine-rich proteins implicated in control of nerve growth and development and regulation of the immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis, with some neoplasms producing SEMA4D in a manner analogous to vascular endothelial growth factor (VEGF) in order to attract Plexin-B1-expressing endothelial cells into the tumor for the purpose of promoting growth and vascularity. While anti-VEGF strategies have been the focus of most angiogenesis inhibition research, such treatment can lead to upregulation of pro-angiogenic factors that can compensate for the loss of VEGF, eventually leading to failure of therapy. Here, we demonstrate that SEMA4D cooperates with VEGF to promote angiogenesis in malignancies and can perform the same function in a setting of VEGF blockade. We also show the potential value of inhibiting SEMA4D/Plexin-B1 signaling as a complementary mechanism to anti-VEGF treatment, particularly in VEGF inhibitor-resistant tumors, suggesting that this may represent a novel treatment for some cancers.
authors.affiliation: Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 West Baltimore Street, 7-North, Baltimore, MD 21201, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Nada O
authors.initials: NO
authors.lastname: Binmadi
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Patrizia
authors.initials: P
authors.lastname: Proia
authors.forename: John R
authors.initials: JR
authors.lastname: Basile
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D039961:Semaphorins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D017931:DNA Primers; D039961:Semaphorins; D042461:Vascular Endothelial Growth Factor A