Imatinib as a key inhibitor of the platelet-derived growth factor receptor mediated expression of cell surface heparan sulfate proteoglycans and functional properties of breast cancer cells.

Abstract

Cell surface heparan sulfate proteoglycans (HSPGs), syndecans and glypicans, play crucial roles in the functional properties of cancer cells, such as proliferation, adhesion, migration and invasion. Platelet-derived growth factor (PDGF)/PDGF receptor (PDGF-R) mediated signaling, on the other hand, is highly associated with cancer progression. Specifically, PDGF-Rα and PDGF-Rβ expressions documented in breast cancer tissue specimens as well as breast cancer cell lines are correlated with tumor aggressiveness and metastasis. Imatinib (Glivec(®)) is a tyrosine kinase inhibitor specific for PDGF-Rs, c-ΚΙΤ and BCR-ABL. In this study we evaluated the effects of imatinib on the properties of breast cancer cells as well as on the expression of HSPGs in the presence and absence of PDGF-BB. These studies have been conducted in a panel of three breast cancer cell lines of low and high metastatic potential. Our results indicate that imatinib exerts a significant inhibitory effect on breast cancer cell proliferation, invasion and migration as well as on the cell surface expression of HSPGs even after exposure of PDGF. These effects depend on the aggressiveness of breast cancer cells and the type of HSPG. It is suggested that imatinib may be of potential therapeutic usefulness in breast cancer regimes.

• Authors: Christina J Malavaki, Andreas E Roussidis, Chrisostomi Gialeli, Dimitris Kletsas, Theodore Tsegenidis, Achileas D Theocharis, George N Tzanakakis, Nikos K Karamanos
• Journal: The FEBS journal (FEBS J) Vol. 280 Issue 10 Pg. 2477-89 (May 2013) ISSN: 1742-4658 [Electronic] England
• PMID: 23374223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors Journal compilation © 2013 FEBS.

Chemical References

• Antineoplastic Agents
• Benzamides
• Cytostatic Agents
• Glypicans
• Ligands
• Piperazines
• Proto-Oncogene Proteins c-sis
• Pyrimidines
• SDC4 protein, human
• Syndecan-4
• Becaplermin
• Imatinib Mesylate
• Receptor, Platelet-Derived Growth Factor alpha
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Antineoplastic Agents (pharmacology)
• Becaplermin
• Benzamides (pharmacology)
• Breast Neoplasms (metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation
• Cytostatic Agents (pharmacology)
• Drug Screening Assays, Antitumor
• Female
• G2 Phase Cell Cycle Checkpoints
• Gene Expression Regulation, Neoplastic (drug effects)
• Glypicans (genetics, metabolism)
• Humans
• Imatinib Mesylate
• Ligands
• M Phase Cell Cycle Checkpoints
• MAP Kinase Signaling System
• MCF-7 Cells
• Neoplasm Invasiveness (pathology, prevention & control)
• Phosphorylation
• Piperazines (pharmacology)
• Proto-Oncogene Proteins c-sis (pharmacology)
• Pyrimidines (pharmacology)
• Receptor, Platelet-Derived Growth Factor alpha (antagonists & inhibitors, metabolism)
• Receptor, Platelet-Derived Growth Factor beta (antagonists & inhibitors, metabolism)
• Signal Transduction
• Syndecan-4 (genetics, metabolism)
• Transcriptome