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CD44v8-10 is a marker for malignant traits and a potential driver of bone metastasis in a subpopulation of prostate cancer cells

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Cancer Biology & Medicine 2021年第3期18卷 788-807页

作者： Rosaria A.Fontanella Silvia Sideri Chiara Di Stefano angiolina catizone Silvia Di Agostino Daniela F.Angelini Gisella Guerrera Luca Battistini Giulia Battafarano Andrea Del Fattore Antonio Francesco Campese Fabrizio Padula Paola De Cesaris Antonio Filippini Anna Riccioli Department of Anatomy HistologyForensic Medicine and OrthopaedicsUnit of Histology and Medical EmbryologySapienza UniversityRome 00161Italy Department of Health Sciences School of Medicine-"Magna Graecia"University of Catanzaro Catanzaro 88100Italy IRCCS Fondazione Santa Lucia Rome 00143 Bone Physiopathology Research Unit Genetics and Rare Diseases Research DivisionBambino GesùChildren’s HospitalIRCCSRome 00146Italy Department of Molecular Medicine Sapienza UniversityRome 00161Italy Department of Life Health and Environmental SciencesUniversity of L’AquilaL'Aquila 67100Italy

Objective:Bone metastasis is a clinically important outcome of prostate carcinoma(PC).We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell *** cells,originated from the spontaneous conversion of a CD44-negative subpopulation,stably express the CD44 v8-10 isoform(CD44 v8-10 pos)and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44 v8-10 ***:Flow cytometry,enzyme-linked immunoassay,immunofluorescence,and Western blot were used for phenotypic and immunologic ***-time quantitative polymerase chain reaction and functional assays were used to assess ***:Analysis of epithelial–mesenchymal transition markers showed that CD44 v8-10 pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry,acquiring bone cell phenotypic and behavioral *** of specific si RNA evidenced the ability of CD44 v8-10 variant to confer osteomimetic features,hence the potential to form bone-specific ***,the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a *** we report that CD44 v8-10 pos cells express programmed death ligand 1,a negative regulator of anticancer immunity,and secrete exceptionally high amounts of interleukin-6,favoring osteoclastogenesis and immunosuppression in bone ***,we identified a novel pathway activated by CD44 v8-10,involving tafazzin(TAZ)and likely the Wnt/TAZ axis,known to play a role in upregulating osteomimetic ***:CD44 v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone.A novel link between TAZ and CD44 v8-10 is also shown.

关键词： Metastasis epithelial phenotype EMT MET IL-6 TAZ

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