title: Over-Expression of the LH Receptor Increases Distant Metastases in an Endometrial Cancer Mouse Model.
abstract: OBJECTIVE
  The aim of the present study was to define the role of luteinizing hormone receptor (LH-R) expression in endometrial cancer (EC), using preclinical mouse models, to further transfer these data to the clinical setting.
  
  
  METHODS
  The role of LH-R over-expression was studied using EC cells (Hec1A, e.g., cells with low endogenous LH-R expression) transfected with the LH-R (Hec1A-LH-R). In vitro cell proliferation was measured through the WST-1 assay, whereas cell invasion was measured trough the matrigel assay. The effects of LH-R over-expression in vivo were analyzed in an appropriately developed preclinical mouse model of EC, which mimicked postmenopausal conditions. The model consisted in an orthotopic xenograft of Hec1A cells into immunodeficient mice treated daily with recombinant LH, to assure high levels of LH.
  
  
  RESULTS
  In vitro data indicated that LH-R over-expression increased Hec1A invasiveness. In vivo results showed that tumors arising from Hec1A-LH-R cells injection displayed a higher local invasion and a higher number of distant metastases, mainly in the lung, compared to tumors obtained from the injection of Hec1A cells. LH withdrawal strongly inhibited local and distant metastatic spread of tumors, especially those arising from Hec1A-LH-R cells.
  
  
  CONCLUSIONS
  The over-expression of the LH-R increases the ability of EC cells to undergo local invasion and metastatic spread. This occurs in the presence of high LH serum concentrations.
authors: Department of Experimental and Clinical Medicine, University of Firenze , Firenze , Italy ; Istituto Toscano Tumori , Firenze , Italy.
authors: Serena
authors: S
authors: Pillozzi
authors: Angelo
authors: A
authors: Fortunato
authors: Emanuele
authors: E
authors: De Lorenzo
authors: Elena
authors: E
authors: Borrani
authors: Massimo
authors: M
authors: Giachi
authors: Gianfranco
authors: G
authors: Scarselli
authors: Annarosa
authors: A
authors: Arcangeli
authors: Ivo
authors: I
authors: Noci
keywords: LH; LH-R; endometrial carcinoma; invasion; metastasis; mouse model