title: Proteomic analysis of zoledronic-acid resistant prostate cancer cells unveils novel pathways characterizing an invasive phenotype.
abstract: Proteomic analysis identified differentially expressed proteins between zoledronic acid-resistant and aggressive DU145R80 prostate cancer (PCa) cells and their parental DU145 cells. Ingenuity Pathway Analysis (IPA) showed a strong relationship between the identified proteins within a network associated with cancer and with homogeneous cellular functions prevalently related with regulation of cell organization, movement and consistent with the smaller and reduced cell-cell contact morphology of DU145R80 cells. The identified proteins correlated in publically available human PCa genomic data with increased tumor expression and aggressiveness. DU145R80 exhibit also a clear increase of alpha-v-(αv) integrin, and of urokinase receptor (uPAR), both included within the same network of the identified proteins. Interestingly, the actin-rich structures localized at the cell periphery of DU145R80 cells are rich of Filamin A, one of the identified proteins and uPAR which, in turn, co-localizes with αv-integrin, in podosomes and/or invadopodia. Notably, the invasive feature of DU145R80 may be prevented by blocking anti-αv antibody. Overall, we unveil a signaling network that physically links the interior of the nucleus via the cytoskeleton to the extracellular matrix and that could dictate PCa aggressiveness suggesting novel potential prognostic markers and therapeutic targets for PCa patients.
authors.affiliation: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Milone
authors.affiliation: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Pucci
authors.affiliation: Neoplastic Progression Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Bifulco
authors.affiliation: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Iannelli
authors.affiliation: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Lombardi
authors.affiliation: Experimental Pharmacology Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciardiello
authors.affiliation: Experimental Pharmacology Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bruzzese
authors.affiliation: Neoplastic Progression Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Carriero
authors.affiliation: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.|Experimental Pharmacology Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
mesh_terms: D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D004164:Diphosphonates / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D012333:RNA, Messenger; D000077211:Zoledronic Acid
keywords: cytoskeleton organization; prostate cancer; urokinase receptor (uPAR); zoledronic acid; αv integrin