Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.
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.
Rafii
Arash
A
UMRS 872 INSERM, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, Equipe 18, Centre de Recherche des Cordeliers, Paris, France.
Mirshahi
Pejman
P
Poupot
Mary
M
Faussat
Anne-Marie
AM
Simon
Anne
A
Ducros
Elodie
E
Mery
Eliane
E
Couderc
Bettina
B
Lis
Raphael
R
Capdet
Jerome
J
Bergalet
Julie
J
Querleu
Denis
D
Dagonnet
Francoise
F
Fournié
Jean-Jacques
JJ
Marie
Jean-Pierre
JP
Pujade-Lauraine
Eric
E
Favre
Gilles
G
Soria
Jeanine
J
Mirshahi
Massoud
M
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
D027425:ATP-Binding Cassette, Sub-Family C Proteins