title: Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion.
abstract: Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell surface antigens that accompany this transition, we studied the changes in cell surface antigenic profiles between a hormone-sensitive prostate cancer line LNCaP and its hormone-refractory derivative C4-2B, using an antibody library-based affinity proteomic approach. We selected a naive phage antibody display library to identify human single-chain antibodies that bind specifically to C4-2B but not LNCaP. Using mass spectrometry, we identified one of the antibody-targeted antigens as the ICAM-1/CD54/human rhinovirus receptor. Recombinant IgG1 derived from this single-chain antibody binds to a neutralizing epitope of ICAM-1 and blocks C4-2B cell invasion through extracellular matrix in vitro. ICAM-1 is thus differentially expressed during the transition of the hormone-sensitive prostate cancer cell line LNCaP to its hormone-refractory derivative C4-2B, plays an important role in imparting the C4-2B line with the ability to invade, and may therefore be a target for therapeutic intervention.
authors.affiliation: Department of Anesthesia, University of California at San Francisco, 1001 Potrero Ave., 3C38, San Francisco, CA 94110, USA.
authors.forename: Fraser
authors.initials: F
authors.lastname: Conrad
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Chalkley
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.forename: James D
authors.initials: JD
authors.lastname: Marks
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D016466:CHO Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D008297:Male; D009361:Neoplasm Invasiveness; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D011485:Protein Binding; D014162:Transfection
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D018931:Antineoplastic Agents, Hormonal; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D019151:Peptide Library; D018799:Intercellular Adhesion Molecule-1