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Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression
M Vasse1, D Thibout, J Paysant
1Laboratoire DIFEMA, Groupe de Recherche MERCI, Faculté de Médecine et Pharmacie de Rouen, 22 Bd Gambetta, 76183 Rouen Cedex, France.
British Journal of Cancer
|March 22, 2001
Summary
Sodium phenylacetate (NaPa) significantly inhibits breast cancer cell invasiveness by increasing adhesion molecules like u-PAR and LFA-1, not by reducing proteases. This finding offers new insights into breast cancer metastasis mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sodium phenylacetate (NaPa) is a phenylalanine metabolite with known cytostatic and antiproliferative effects.
- Breast cancer cell invasiveness is a critical factor in metastasis and is influenced by proteases and cell adhesion molecules.
Purpose of the Study:
- To investigate the effect of NaPa on the invasiveness of breast cancer cell lines (MDA-MB-231, MCF-7, MCF-7 ras).
- To elucidate the mechanisms underlying NaPa's impact on cell invasiveness, focusing on urokinase plasminogen activator (u-PA), its receptor (u-PAR), matrix metalloproteinases (MMPs), and cell adhesion molecules.
Main Methods:
- Treatment of breast cancer cell lines (MDA-MB-231, MCF-7, MCF-7 ras) with NaPa.
- Assessment of cell invasiveness using Matrigel.
- Analysis of u-PA expression, u-PAR expression, MMP secretion, and cell adhesion to vitronectin.
- Evaluation of Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1) expression.
- Use of neutralizing antibodies against LFA-1 to confirm its role.
Main Results:
- NaPa strongly inhibited MDA-MB-231 cell invasiveness through Matrigel (86% inhibition at 20 mM).
- NaPa increased u-PAR and MMP-9 secretion in MDA-MB-231 cells, and enhanced adhesion to vitronectin.
- NaPa upregulated LFA-1 and ICAM-1 expression in MDA-MB-231 cells, with a delayed effect in MCF-7 and MCF-7 ras cells.
- Neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells.
Conclusions:
- The inhibition of MDA-MB-231 cell invasiveness by NaPa is primarily mediated by increased expression of adhesion molecules (u-PAR, LFA-1) rather than a decrease in proteases (u-PA, MMPs).
- NaPa's effects on cell structure and adhesion molecules contribute to its anti-invasive properties in breast cancer.
- These findings suggest LFA-1 plays a crucial role in NaPa-mediated inhibition of breast cancer cell invasion.