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The FN13 peptide inhibits human tumor cells invasion through the modulation of alpha v beta 3 integrins organization and the inactivation of ILK pathway.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2007 Jun; Vol. 1773 (6), pp. 747-63. Date of Electronic Publication: 2007 Feb 24. - Publication Year :
- 2007
-
Abstract
- We report the effect of the stable expression of a 13 amino acid human fibronectin (FN) peptide (FN13) on the organization of the FN extracellular matrix (ECM) and of FN integrin receptors (FNRs), in relationship with the inhibition of cellular invasion, in three FN-ECM defective human tumor-derived cell lines: SK-Hep1C3, hepatoma, ACN, neuroblastoma, and SK-OV-3, ovary carcinoma. All these cell lines stably expressing the FN13 peptide, organized an FN-ECM, disorganized alpha v beta 1 integrins and inactivated the ILK pathway, with the loss of secretion of MMP-9. This was associated with the inhibition of cell invasion in Matrigel matrix only in SK-Hep1C3 and ACN, but not in SK-OV-3 cells. Analysis of the integrin receptors organization showed that the FN13 expressing cells SK-Hep1C3 and ACN organized alpha v beta 3 integrins, whereas SK-OV-3 organized alpha v beta 5 dimers. The functional block of alpha v beta 5 integrins, with an inactivating anti-alpha v beta 5 antibody, led to the induction of alpha v beta 3 integrins also in SK-OV-3 cells, and to the inhibition of cell invasion. These data show that in the human tumor cells studied FN13 inhibits the in vitro invasion through the dissociation of alpha v beta 1 dimers, leading to ILK pathway inactivation, only when the organization of alpha v beta 3 integrins is induced in the plasma membrane.
- Subjects :
- Cell Line, Tumor
Cell Membrane genetics
Cell Membrane metabolism
Cell Membrane pathology
Dimerization
Fibronectins genetics
Gene Expression Regulation, Neoplastic
Humans
Matrix Metalloproteinase 9 metabolism
Neoplasm Invasiveness
Neoplasm Proteins genetics
Neoplasms genetics
Neoplasms pathology
Peptides genetics
Protein Serine-Threonine Kinases genetics
Fibronectins biosynthesis
Integrin alphaVbeta3 metabolism
Neoplasm Proteins metabolism
Neoplasms enzymology
Peptides metabolism
Protein Serine-Threonine Kinases metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1773
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 17383746
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2007.02.007