title: Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment.
abstract: Angiogenesis is critical for tumor growth and survival and involves interactions between cancer and endothelial cells. Prostate-specific membrane antigen (PSMA/FOLH1) is expressed in the neovasculature of several types of cancer. However, the study of neovascular PSMA expression has been impeded as human umbilical vein endothelial cell (HUVEC) cultures are PSMA-negative and both tumor xenografts and patient-derived xenograft (PDX) models are not known to express PSMA in their vasculature. Therefore, PSMA expression was examined in HUVECs, in vitro and in vivo, and we tested the hypothesis that cancer cell-HUVEC crosstalk could induce the expression of PSMA in HUVECs. Interestingly, conditioned media from several cancer cell lines induced PSMA expression in HUVECs, in vitro, and these lines induced PSMA, in vivo, in a HUVEC coimplantation mouse model. Furthermore, HUVECs in which PSMA expression was induced were able to internalize J591, a mAb that recognizes an extracellular epitope of PSMA as well as nanoparticles bearing a PSMA-binding ligand/inhibitor. These findings offer new avenues to study the molecular mechanism responsible for tumor cell induction of PSMA in neovasculature as well as the biological role of PSMA in neovasculature. Finally, these data suggest that PSMA-targeted therapies could synergize with antiangiogenic and/or other antitumor agents and provide a promising model system to test therapeutic modalities that target PSMA in these settings.
  
  
  
  Cancer cells are able to induce PSMA expression in HUVECs, in vitro and in vivo, allowing internalization of PSMA-specific mAbs and nanoparticles bearing a PSMA-binding ligand/inhibitor. Mol Cancer Res; 14(11); 1045-53. ©2016 AACR.
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York. daniel.nguyen@insel.ch nhbander@med.cornell.edu.|Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Nguyen
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Xiong
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Samuel
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Wilhem
authors.initials: W
authors.lastname: Leconet
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Vincent
authors.initials: V
authors.lastname: Navarro
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moy
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Sae
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Marigdalia K
authors.initials: MK
authors.lastname: Ramirez-Fort
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York.
authors.forename: Jaspreet S
authors.initials: JS
authors.lastname: Batra
authors.affiliation: Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York. daniel.nguyen@insel.ch nhbander@med.cornell.edu.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D000939:Epitopes / Q000276:immunology; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D017077:Culture Media, Conditioned; D000939:Epitopes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II