Tumor-derived EMMPRIN (Extracellular Matrix Metalloproteinase Inducer) Stimulates Collagenase Transcription Through MAPK p38

FEBS Lett. 1998 Dec 11;441(1):88-92. doi: 10.1016/s0014-5793(98)01474-4.

Abstract

EMMPRIN (extracellular matrix metalloproteinase inducer) stimulates fibroblast metalloproteinases (MMP) 1, 2 and 3 (Kataoka et al. (1993) Cancer Res. 53, 3154-3158). Here we focus on MMP-1, showing that in lung tumors, MMP-1's cognate mRNA is strongly expressed in stromal fibroblasts adjacent to EMMPRIN-expressing tumor cells. In vitro, EMMPRIN upregulates MMP-1 mRNA expression in a concentration-dependent manner, with a peak accumulation at 24 h. The response is genistein-sensitive, suggesting it is dependent on tyrosine kinase activity. Analysis of tyrosine phosphorylation-dependent MAP kinases ERK 1/2, SAPK/JNK, and p38 showed that the activity of p38 but not that of the other 2 kinases was elevated in response to EMMPRIN. That p38 activity was required for EMMPRIN stimulation of MMP-1 was evident from results showing that the p38 inhibitor SB203580 blocked this response. This is the first available information regarding the mechanism by which tumor-associated molecules upregulate MMP synthesis in stromal fibroblasts.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD*
  • Antigens, Neoplasm*
  • Basigin
  • Biomarkers, Tumor
  • Bronchi / enzymology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line
  • Collagenases / genetics*
  • Epithelial Cells / enzymology
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kinetics
  • Lung / metabolism
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics*
  • Matrix Metalloproteinase 1
  • Membrane Glycoproteins / metabolism*
  • Mitogen-Activated Protein Kinases*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription, Genetic*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • BSG protein, human
  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • RNA, Messenger
  • Basigin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Collagenases
  • Matrix Metalloproteinase 1