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Platelets increase survival of adenocarcinoma cells challenged with anticancer drugs: mechanisms and implications for chemoresistance

Lookup NU author(s): Dr Achim Treumann, Dr Howsun Jow


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BACKGROUND 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.

Publication metadata

Author(s): Radziwon-Balicka A, Medina C, O'Driscoll L, Treumann A, Bazou D, Inkielewicz-Stepniak I, Radomski A, Jow H, Radomski MW

Publication type: Article

Publication status: Published

Journal: British Journal of Pharmacology

Year: 2012

Volume: 167

Issue: 4

Pages: 787-804

Print publication date: 25/09/2012

ISSN (print): 0007-1188

ISSN (electronic): 1476-5381

Publisher: John Wiley & Sons Ltd.


DOI: 10.1111/j.1476-5381.2012.01991.x

PubMed id: 22506717


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Funder referenceFunder name
08/SRC/B1410Science Foundation Ireland (SFI)
O5/FE1/B862Science Foundation Ireland (SFI)