Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor beta-3

Fertil Steril. 2010 Mar 15;93(5):1500-8. doi: 10.1016/j.fertnstert.2009.01.081. Epub 2009 Mar 27.

Abstract

Objective: To examine the effect of transforming growth factor (TGF) beta3 on immortalized myometrial and leiomyoma cell lines cloned from primary cell cultures of surgical specimens, and to determine whether such treatment alters myometrial cell extracellular matrix (ECM) expression.

Design: Laboratory study.

Setting: University hospital.

Patient(s): Immortalized myometrial and leiomyoma cells from patients with symptomatic leiomyomata.

Intervention(s): Tissue culture, followed by cellular, RNA, and protein analysis.

Main outcome measure(s): Cell proliferation, alteration in ECM component expression.

Result(s): Immortalized leiomyoma and myometrial cells demonstrate increased mRNA and protein production of the ECM proteins, collagen 1A1 (15.0-fold), fibronectin 1 (2.93 fold), and connective tissue growth factor (9.40-fold) with exogenous TGF-beta3 stimulation. Notably, the expression of collagen 1A1, fibronectin 1, and connective tissue growth factor in myometrial cells increase to similar expression levels as those found in leiomyoma cells. In addition, TGF-beta3 decreased production of genes involved in matrix resorption, including matrix metalloproteinase 2 (0.65-fold) and -11 (0.68-fold).

Conclusion(s): TGF-beta3 induced a molecular phenotype in myometrial cells that was similar to leiomyoma cells, with elevated production of ECM-related genes and decreased production of ECM degradation-related genes.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Connective Tissue Growth Factor / metabolism
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Fibronectins / metabolism
  • Fibrosis
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leiomyoma / genetics
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Matrix Metalloproteinase 11 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Myometrium / metabolism*
  • Myometrium / pathology
  • Phenotype
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta3 / metabolism*
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • CCN2 protein, human
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Extracellular Matrix Proteins
  • Fibronectins
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta3
  • Connective Tissue Growth Factor
  • MMP11 protein, human
  • Matrix Metalloproteinase 11
  • MMP2 protein, human
  • Matrix Metalloproteinase 2