title: Platelets increase survival of adenocarcinoma cells challenged with anticancer drugs: mechanisms and implications for chemoresistance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Radziwon-Balicka
authors.forename: C
authors.initials: C
authors.lastname: Medina
authors.forename: L
authors.initials: L
authors.lastname: O'Driscoll
authors.forename: A
authors.initials: A
authors.lastname: Treumann
authors.forename: D
authors.initials: D
authors.lastname: Bazou
authors.forename: I
authors.initials: I
authors.lastname: Inkielewicz-Stepniak
authors.forename: A
authors.initials: A
authors.lastname: Radomski
authors.forename: H
authors.initials: H
authors.lastname: Jow
authors.forename: M W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D017239:Paclitaxel / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel; D005472:Fluorouracil