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

Autor: Dimitris Kletsas, Achileas D. Theocharis, Chrisostomi Gialeli, Christina J. Malavaki, Nikos K. Karamanos, Theodore Tsegenidis, Andreas E. Roussidis, George N. Tzanakakis
Rok vydání: 2013
Předmět:
medicine.medical_specialty
Receptor
Platelet-Derived Growth Factor alpha
MAP Kinase Signaling System
medicine.drug_class
Becaplermin
Antineoplastic Agents
Breast Neoplasms
Biology
Ligands
Biochemistry
Piperazines
Tyrosine-kinase inhibitor
Metastasis
Receptor
Platelet-Derived Growth Factor beta
Breast cancer
Glypicans
Cell Movement
Internal medicine
medicine
Humans
Neoplasm Invasiveness
Phosphorylation
Molecular Biology
Cell Proliferation
Cell growth
Cancer
Proto-Oncogene Proteins c-sis
Cell Biology
Cytostatic Agents
medicine.disease
G2 Phase Cell Cycle Checkpoints
Gene Expression Regulation
Neoplastic
carbohydrates (lipids)
Pyrimidines
Imatinib mesylate
Endocrinology
Benzamides
Cancer cell
Imatinib Mesylate
MCF-7 Cells
Cancer research
biology.protein
M Phase Cell Cycle Checkpoints
Female
Syndecan-4
Drug Screening Assays
Antitumor
Transcriptome
Platelet-derived growth factor receptor
Signal Transduction
Zdroj: FEBS Journal. 280:2477-2489
ISSN: 1742-464X
DOI: 10.1111/febs.12163
Popis: 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.
Databáze: OpenAIRE
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