title: Microsatellite instable and microsatellite stable primary endometrial carcinoma cells and their subcutaneous and orthotopic xenografts recapitulate the characteristics of the corresponding primary tumor.
abstract: OBJECTIVE
  Well-characterized, low-passage, primary cell cultures established directly from patient tumors are an important tool for drug screening because these cultures faithfully recapitulate the genomic features of primary tumors. Here, we aimed to establish these cell cultures from primary endometrial carcinomas (ECs) and to develop subcutaneous and orthotopic xenograft models as a model to validate promising treatment options for EC in the in vivo setting.
  
  
  METHODS
  Primary cell cultures of EC tumors were established and validated by analysing histologic and genetic characteristics, telomerase activity, and in vitro and in vivo growth characteristics. Using these primary cell cultures, subcutaneous and orthotopic mouse models were subsequently established.
  
  
  RESULTS
  We established and characterized 7 primary EC cell cultures and corresponding xenograft models of different types of endometrioid tumors. Interestingly, we observed that the chance to successfully establish a primary cell culture seems higher for microsatellite instable than microsatellite stable tumors. For the first time, we also established an orthotopic murine model for EC derived from a primary cell culture. In contrast to EC cell lines, grafted tumor cultures preserved the original tumor structure and mimicked all histologic features. They also established abdominal and distant metastases, reflecting the tumorigenic behavior in the clinical setting. Remarkably, the established cell cultures and xenograft tumors also preserved the genetic characteristics of the primary tumor.
  
  
  CONCLUSIONS
  The established EC cultures reflect the epithelial genetic characteristics of the primary tumor. Therefore, they provide an appropriate model to investigate EC biology and apply high-throughput drug screening experiments. In addition, the established murine xenograft models, in particular the orthotopic model, will be useful to validate promising therapeutic strategies in vivo, as the grafted tumors closely resemble the primary tumors from which they were derived. Microsatellite instable status seems to determine the success rate of establishing primary cell cultures.
authors.affiliation: *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospitals Gasthuisberg; †Department of Oncology, Laboratory for Translational Genetics, KU Leuven; and ‡Vesalius Research Center (VRC), VIB, Leuven; and §Department of Gynecology, AZ Groeninge Hospital, Kortrijk, Belgium.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schrauwen
authors.forename: Lieve
authors.initials: L
authors.lastname: Coenegrachts
authors.forename: Jeroen
authors.initials: J
authors.lastname: Depreeuw
authors.forename: Catherina
authors.initials: C
authors.lastname: Luyten
authors.forename: Godelieve
authors.initials: G
authors.lastname: Verbist
authors.forename: David
authors.initials: D
authors.lastname: Debruyne
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000556:secondary; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007633:Keratins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D061251:Primary Cell Culture; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014746:Vimentin; D007633:Keratins