Effects of EGF and TGF-alpha on Invasion and Proteinase Expression of Uterine Cervical Adenocarcinoma OMC-4 Cells

Invasion Metastasis. 1998-1999;18(4):176-83. doi: 10.1159/000024510.

Abstract

Uterine cervical adenocarcinoma typically is an aggressive neoplasm with a propensity for early invasion and dissemination; however, the regulatory mechanism of invasive activity of cervical adenocarcinoma cells has not been fully understood. In this study, biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on invasion and proteinase expression of human cervical adenocarcinoma OMC-4 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into the reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. Their effects on tumor cell migration were also confirmed by wound assay. The zymography of tumor-conditioned medium showed that the treatment of OMC-4 cells with EGF and TGF-alpha resulted in the increase of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (uPA). Matrilysin (MMP-7), also secreted by OMC-4 cells, was not affected by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion of cervical adenocarcinoma cells, which may be associated with their stimulatory effects on tumor cell motility and the induction of type IV collagenase and uPA secreted by tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Caseins / metabolism
  • Cell Movement / drug effects
  • Collagen / metabolism
  • Drug Combinations
  • Endopeptidases / biosynthesis*
  • Endopeptidases / genetics
  • Enzyme Induction / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Female
  • Fibrinogen / metabolism
  • Gelatin / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Laminin / metabolism
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinases / biosynthesis
  • Matrix Metalloproteinases / genetics
  • Neoplasm Invasiveness*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Proteoglycans / metabolism
  • Transforming Growth Factor alpha / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Caseins
  • Drug Combinations
  • Laminin
  • Neoplasm Proteins
  • Proteoglycans
  • Transforming Growth Factor alpha
  • matrigel
  • Epidermal Growth Factor
  • Gelatin
  • Fibrinogen
  • Collagen
  • Endopeptidases
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 7