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Metalloproteinases as key molecules to target invasiveness in solid tumors
Author(s) -
Karamanos Nikos K,
Staxtea Xanthi,
Gialeli Chrisostomi
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb268
Subject(s) - paracrine signalling , cancer research , matrix metalloproteinase , metastasis , cancer cell , colorectal cancer , extracellular matrix , stromal cell , cancer , biology , chemistry , microbiology and biotechnology , receptor , biochemistry , genetics
Metastasis of cancer cells requires degradation of the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are the principal ECM‐degrading enzymes. Paracrine interactions between stroma fibroblasts and cancer cells are also involved in the expression and activity of MMPs. The aim of this study was to examine whether gene expression of MMPs is related with the invasive potential of colon cancer. In vitro studies on a panel of cell lines in the presence specific tyrosine kinase inhibitors and monoclonal antibodies were performed. The results showed that the invasive properties of cancer cells are associated with significant changes in gene expression of MT1‐MMP and MMP‐2. The expression of MT1 from HT‐29 colon cancer cells is increased by the conditioned media (CM) obtained by fibroblasts. MT1 contributes to the activation of proMMP‐2. STI571 suppressed the expression of MT1 in HT‐29 colon cancer cells as well as pro‐ and active MMP‐2. Panitumumab that target EGF‐R in colon cancer affects also the expression of MMPs. It is concluded that paracrine interactions is a determining factor for tumor cell behavior and suppression of certain MMPs may be of great value in molecular targeted therapy.