title: Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.
abstract: BACKGROUND
  The microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.
  
  
  RESULTS
  We isolated an original type of stromal cells, referred to as "Hospicells" from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.
  
  
  CONCLUSIONS
  This is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient's tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.
authors.affiliation: UMRS 872 INSERM, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, Equipe 18, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
authors.forename: Pejman
authors.initials: P
authors.lastname: Mirshahi
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faussat
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Elodie
authors.initials: E
authors.lastname: Ducros
authors.forename: Eliane
authors.initials: E
authors.lastname: Mery
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
authors.forename: Raphael
authors.initials: R
authors.lastname: Lis
authors.forename: Jerome
authors.initials: J
authors.lastname: Capdet
authors.forename: Julie
authors.initials: J
authors.lastname: Bergalet
authors.forename: Denis
authors.initials: D
authors.lastname: Querleu
authors.forename: Francoise
authors.initials: F
authors.lastname: Dagonnet
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marie
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Gilles
authors.initials: G
authors.lastname: Favre
authors.forename: Jeanine
authors.initials: J
authors.lastname: Soria
authors.forename: Massoud
authors.initials: M
authors.lastname: Mirshahi
mesh_terms: D000368:Aged; D001681:Biological Assay; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002469:Cell Separation; D019008:Drug Resistance, Neoplasm; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D010641:Phenotype; D017154:Stromal Cells / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins