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dc.contributor.authorO'Driscoll, Lorraineen
dc.contributor.authorMedina Martin, Carlosen
dc.date.accessioned2014-10-14T11:21:05Z
dc.date.available2014-10-14T11:21:05Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationRadziwon-Balicka A, Medina C, O'Driscoll L, Treumann A, Bazou D, Inkielewicz-Stepniak I, Radomski A, Jow H, Sawicki G, Radomski MW., Platelets increase survival of adenocarcinoma cells challenged with anticancer drugs: mechanisms and implications for chemoresistance., Brit. J. Pharmacol., 167, 4, 2012, 787 - 804en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/71509
dc.descriptionPUBLISHEDen
dc.description.abstractBACKGROUND AND PURPOSE: Cancer cells grow without the restraints of feedback control mechanisms, leading to increased cancer cell survival. The treatment of cancer is often complicated by the lack of response to chemotherapy leading to chemoresistance and persistent survival of tumour cells. In this work we studied the role of platelets in chemotherapy-induced cancer cell death and survival. EXPERIMENTAL APPROACH: Human adenocarcinoma cells, colonic (Caco-2) and ovarian (59 M) cells, were incubated with 5-fluorouracil (1-300 µg·mL(-1) ) or paclitaxel (1-200 µg·mL(-1) ) in the presence or absence of platelets (1.5 × 10(8) mL(-1) ) for 1, 24 or 72 h. Following incubation, cancer cells were harvested and cell survival/death was assayed using flow cytometry, Western blotting, real-time PCR, TaqMan® Gene Expression Assays and proteomics. KEY RESULTS: Human platelets increased the survival of colonic and ovarian adenocarcinoma cells treated with two standard anticancer drugs, 5-fluorouracil and paclitaxel. In the presence of platelets, cancer cells up-regulated anti-apoptotic and down-regulated pro-apoptotic genes, increased the number of cells in the synthesis of DNA and decreased the number in the quiescent phase, increased expression of cyclins, DNA repair proteins and MAPKs. The analysis of platelet-Caco-2 secretome demonstrated the release of the chemokine RANTES, thrombospondin-1, TGF-β and clusterin. Finally, human recombinant RANTES and thrombospondin-1 improved survival of Caco-2 cells challenged with paclitaxel. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that platelets increase adenocarcinoma cells survival, proliferation and chemoresistance to standard anticancer drugs. Modulating cancer cell-platelet interactions may offer a new strategy to improve the efficacy of chemotherapy.en
dc.format.extent787en
dc.format.extent804en
dc.language.isoenen
dc.relation.ispartofseriesBrit. J. Pharmacol.en
dc.relation.ispartofseries167en
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectCancer cellsen
dc.titlePlatelets increase survival of adenocarcinoma cells challenged with anticancer drugs: mechanisms and implications for chemoresistance.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lodriscen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/martinc2en
dc.identifier.rssinternalid92855en
dc.identifier.doi10.1111/j.1476-5381.2012.01991.xen
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumberO5/FE1/B862en
dc.contributor.sponsorGrantNumber08/SRC/B1410en
dc.relation.sourcehttp://www.ncbi.nlm.nih.gov/pubmed/22506717en
dc.subject.TCDThemeCanceren
dc.subject.TCDTagDrug development and evaluationen
dc.identifier.rssurihttp://www.ncbi.nlm.nih.gov/pubmed/22506717en
dc.identifier.orcid_id0000-0002-9860-8262en


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