Abstract
Co-culture of periodontal ligament (PDL) fibroblasts and SCC-25 oral squamous carcinoma cells (OSCC), results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs). Paracrin circuits between CAFs and OSCC cells were hypothesized to regulate the gene expression of matrix remodeling enzymes in their co-culture, which was performed for 7days, followed by analysis of the mRNA/protein expression and activity of metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and other relevant genes. Interleukin1-β, transforming growth factor-β1, fibronectin and αvβ6 integrin have shown to be involved in the regulation of the MMP and TIMP gene expression in co-culture of CAFs and tumor cells. In addition, these cells also cooperated in activation of MMP pro-enzymes. It is particularly interesting that the fibroblast-produced inactive MMP-2 has been activated by the tumor-cell-produced membrane-type 1 matrix metalloproteinase (MT1-MMP). The crosstalk between cancer- and the surrounding fibroblast stromal-cells is essential for the fine tuning of cancer cells invasivity.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Carcinoma, Squamous Cell / genetics
-
Carcinoma, Squamous Cell / metabolism*
-
Carcinoma, Squamous Cell / pathology
-
Cell Line, Tumor
-
Cells, Cultured
-
Coculture Techniques
-
Fibroblasts / metabolism
-
Fibroblasts / pathology
-
Gene Expression Regulation, Enzymologic
-
Gene Expression Regulation, Neoplastic
-
Humans
-
Matrix Metalloproteinase 14 / genetics
-
Matrix Metalloproteinase 14 / metabolism
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 2 / metabolism
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism
-
Matrix Metalloproteinases / genetics
-
Matrix Metalloproteinases / metabolism*
-
Models, Biological
-
Mouth Neoplasms / genetics
-
Mouth Neoplasms / metabolism*
-
Mouth Neoplasms / pathology
-
Neoplasm Invasiveness
-
Paracrine Communication
-
Periodontal Ligament / metabolism
-
Periodontal Ligament / pathology
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
RNA, Neoplasm / genetics
-
RNA, Neoplasm / metabolism
-
Tissue Inhibitor of Metalloproteinases / genetics
-
Tissue Inhibitor of Metalloproteinases / metabolism*
Substances
-
RNA, Messenger
-
RNA, Neoplasm
-
Tissue Inhibitor of Metalloproteinases
-
Matrix Metalloproteinases
-
MMP2 protein, human
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9
-
MMP14 protein, human
-
Matrix Metalloproteinase 14