title: Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis.
abstract: Lysyl oxidases (LOXs) are enzymes involved in collagen deposition, extracellular membrane remodeling, and invasive/metastatic potential. Previous studies reveal an association of LOXs and endometriosis. We aimed to identify the mechanisms activated by upregulation of lysyl oxidases (LOX) in endometriotic cells and tissues. We hypothesized that LOX plays a role in endometriosis by promoting invasiveness and epithelial to mesenchymal transition (EMT).
  
  
  METHODS
  The LOX protein expression levels were measured by immunohistochemistry in lesions and endometrium on a tissue microarray (TMA) and in endometrial biopsies from patients and controls during the window of implantation (WOI). Estradiol regulation of LOX expression was determined by quantitative polymerase chain reaction (qPCR). Proliferation, invasion, and migration assays were performed in epithelial (endometrial epithelial cell), endometrial (human endometrial stromal cell), and endometriotic cell lines (ECL and 12Z). Pathway-focused multiplex qPCR was used to determine transcriptome changes due to LOX overexpression.
  
  
  RESULTS
  LOX protein was differentially expressed in ovarian versus peritoneal lesions. During WOI, LOX levels were higher in luminal epithelium of patients with endometriosis-associated infertility compared to controls. Invasive epithelial cell lines expressed higher levels of LOX than noninvasive ones. Transfection of LOX into noninvasive epithelial cells increased their migration in an LOX inhibitor-sensitive manner. Overexpression of LOX did not fully induce EMT but the expression of genes related to fibrosis and extracellular matrix remodeling were dysregulated.
  
  
  CONCLUSIONS
  This study documents that expression of LOX is differentially regulated in endometriotic lesions and endometrium. A role for LOX in mediating proliferation, migration, and invasion of endometrial and endometriotic cells was observed, which may be implicated in the establishment and progression of endometriotic lesions.
authors.affiliation: Department of Anatomy, Ponce Health Sciences University-School of Medicine & Ponce Research Institute, Ponce, PR, USA.
authors.forename: Lynnette A
authors.initials: LA
authors.lastname: Ruiz
authors.affiliation: Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Perla M
authors.initials: PM
authors.lastname: Báez-Vega
authors.affiliation: Department of Microbiology, Ponce Health Sciences University-School of Medicine & Ponce Research Institute, Ponce, PR, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Department of Development and Regeneration, University Hospital Leuven, Leuven, Belgium.
authors.forename: Daniëlle P
authors.initials: DP
authors.lastname: Peterse
authors.affiliation: Department of Biochemistry, Ponce Health Sciences University- School of Medicine & Ponce Research Institute, Ponce, PR, USA.
authors.forename: Janice B
authors.initials: JB
authors.lastname: Monteiro
authors.affiliation: Department of Ob-Gyn, University of Puerto Rico - Medical Sciences Campus, Genes Fertility Institute, San Juan, PR, USA.
authors.forename: Nabal
authors.initials: N
authors.lastname: Bracero
authors.affiliation: Puerto Rico Fertility Center, Bayamón, PR, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Beauchamp
authors.affiliation: Department of Ob-Gyn & Reproductive Biology, Michigan State University, Grand Rapids, MI, USA.
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
authors.affiliation: Department of Microbiology, Department of Ob-Gyn, Ponce Health Sciences University-School of Medicine & Ponce Research Institute, Ponce, PR, USA iflores@psm.edu.
authors.forename: Idhaliz
authors.initials: I
authors.lastname: Flores
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D004715:Endometriosis / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D016133:Polymerase Chain Reaction; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D015398:Signal Transduction; D046888:Tissue Array Analysis; D059467:Transcriptome; D014162:Transfection
chemical_list: D004958:Estradiol; D008249:Protein-Lysine 6-Oxidase
keywords: endometriosis; endometrium; epithelial to mesenchymal transition; infertility; lysyl oxidase