MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells

Mol Cell Endocrinol. 2015 Mar 15:404:113-22. doi: 10.1016/j.mce.2015.01.037. Epub 2015 Jan 30.

Abstract

The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion.

Keywords: Calpain; MMP2; MMP9; Migration and invasion; Sphingosine 1-phosphate; Thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / enzymology
  • Adenocarcinoma, Follicular / pathology*
  • Calpain / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Lysophospholipids / pharmacology*
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / pathology*
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Lysophospholipids
  • RAC1 protein, human
  • sphingosine 1-phosphate
  • Calpain
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • rac1 GTP-Binding Protein
  • Sphingosine