Τίτλος:
Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy.
Συγγραφείς:
Kharaziha, P.
Chioureas, D.
Rutishauser, D.
Baltatzis, G.
Lennartsson, L.
Fonseca, P.
Azimi, A.
Hultenby, K.
Zubarev, R.
Ullén, A.
Yachnin, J.
Nilsson, S.
Panaretakis, T.
Περιοδικό:
OncoTargets and therapy
Εκδότης:
Impact Journals, LLC
Λέξεις-κλειδιά:
binding protein; docetaxel; endophilin; endophilin A2; multidrug resistance protein 1; multidrug resistance protein 3; protein PABP4; unclassified drug; ABCB1 protein, human; antineoplastic agent; cabazitaxel; docetaxel; multidrug resistance protein; multidrug resistance protein 3; nanoparticle; PABPC4 protein, human; plasma protein; polyadenylic acid binding protein; proteome; SH3GL1 protein, human; signal peptide; taxoid; tumor marker, adult; aged; Article; castration resistant prostate cancer; clinical article; controlled study; degradation; drug response; drug sensitivity; exosome; extracellular matrix; human; human cell; male; middle aged; molecular biology; multiple cycle treatment; prostate cancer; protein expression; proteomics; randomized controlled trial (topic); Western blotting; biology; cell death; chemistry; cohort analysis; drug effects; drug resistance; exosome; metabolism; prostate tumor; Prostatic Neoplasms, Castration-Resistant; randomized controlled trial; tumor cell line, Antineoplastic Agents; Biomarkers, Tumor; Blood Proteins; Cell Death; Cell Line, Tumor; Cohort Studies; Computational Biology; Drug Resistance, Neoplasm; Exosomes; Extracellular Matrix; Humans; Intracellular Signaling Peptides and Proteins; Male; Nanoparticles; P-Glycoproteins; Poly(A)-Binding Proteins; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Proteome; Taxoids
DOI:
10.18632/oncotarget.3226
