title: An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis.
abstract: Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries. Metastasis is the major cause of endometrial cancer deaths. Therefore, there is a vital need for clinically relevant in vivo models allowing the elucidation of the molecular and cellular mechanisms underlying metastatic behavior. In this study, we describe an innovative experimental orthotopic model of human endometrial carcinoma. Implantation in the bifurcation of the uterine horns resulted in tumors integrated into the myometrial compartment, which can be used and further exploited for the study of in vivo angiogenesis, myometrial invasion, and the metastatic capacity of endometrial cancer cells. This orthotopic model also represents a suitable tool to analyze how tumorigenesis and distant metastasis of endometrial cancer might be influenced by gene alteration, by modulating its expression in the original cancer cell line. One of the candidate genes implicated in endometrial cancer is the transcription factor RUNX1. The over-expression of RUNX1 in the endometrial cancer cell line HEC1A and the transplantation of these cells to the uterus of nude mice were associated specifically with distant metastasis in the lung. RUNX1 plays a role in the establishment of metastases in endometrial cancer. Translated to the clinics, these models would be equivalent to an advanced undifferentiated carcinoma with node affectation (stage IIIC) and distant metastasis (stage IVB). These patients would be candidates for adjuvant therapy, not efficient until today, and therefore, our models are actually suitable for the design and evaluation of experimental therapies.
authors.affiliation: Biomedical Research Unit, Vall d'Hebron Research Institute, University Hospital, Barcelona, Spain.
authors.forename: Andreas
authors.initials: A
authors.lastname: Doll
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.forename: Marta
authors.initials: M
authors.lastname: Llaurado
authors.forename: Marina
authors.initials: M
authors.lastname: Rigau
authors.forename: Eva
authors.initials: E
authors.lastname: Colas
authors.forename: Marta
authors.initials: M
authors.lastname: Monge
authors.forename: Jordi
authors.initials: J
authors.lastname: Xercavins
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Berta
authors.initials: B
authors.lastname: Diaz
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Moreno
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventos
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D017931:DNA Primers; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; C493726:Runx1 protein, mouse