title: Anti-caveolin-1 antibodies as anti-prostate cancer therapeutics.
abstract: Caveolae are critical cell surface structures important in coordinated cell signaling and endocytosis. One of the major proteins of caveolae is caveolin 1 (Cav-1). Cellular levels of Cav-1 are associated with cancer progression. In prostate cancer cells, levels of Cav-1 are positively correlated with tumor progression and metastasis. Cav-1 can be secreted by prostate cancer cells into the microenvironment and triggers proliferation and anti-apoptosis of the tumor and tumor endothelial cells. Clinical studies have shown increased serum Cav-1 levels in patients with poor prognosis. In tissue culture and animal model experiments, blocking secreted Cav-1 by polyclonal antibodies inhibits tumor cell growth. Cav-1 is therefore a potential therapeutic target for prostate cancer treatment. In this study, we used Cav-1 knock-out mice as hosts to produce monoclonal anti-Cav-1 antibodies. A total of 11 hybridoma cell lines were selected for their ability to produce antibodies that bound GST-Cav-1 but not GST on glutathione-coated ELISA plates. Further screening with ELISAs using GST-Cav-1 fragments on GSH-coated plates classified these antibodies into four groups: N1-31 with five antibodies binds the far N-terminus between amino acids 1 and 31; N32-80 with three antibodies binds between amino acids 32 and 80; CSD with two antibodies potentially bind the scaffolding domain (amino acids 80-101); and Cav-1-C with 1 antibody binds parts of the C-terminal half. Binding affinities (Kd) of these antibodies to soluble Cav-1 ranged from 10(-11) to 10(-8) M. Binding competition experiments revealed that these antibodies recognized a total of six different epitopes on Cav-1. Potency of these antibodies to neutralize Cav-1-mediated signaling pathways in cultured cells and in animal models will be tested. A selected monoclonal antibody will then be humanized and be further developed into a potential anti-prostate cancer therapeutic.
authors.affiliation: Cancer Research Institute, Department of Medicine, Scott & White Hospital, Texas A&M University Health Science Center, Temple, Texas 76502, USA.
authors.forename: Shu-Ru
authors.initials: SR
authors.lastname: Kuo
authors.forename: Salahaldin A
authors.initials: SA
authors.lastname: Tahir
authors.forename: Sanghee
authors.initials: S
authors.lastname: Park
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
authors.forename: Scott
authors.initials: S
authors.lastname: Coffield
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
authors.forename: Jen-Sing
authors.initials: JS
authors.lastname: Liu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000918:Antibody Specificity; D051242:Caveolin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D051242:Caveolin 1; D011994:Recombinant Proteins