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
(2013) In FEBS Journal 280(10). p.2477-2489- 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... (More)
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. PDGF/PDGF-R-mediated signaling axis is highly associated with cancer progression. The regulatory role of PDGF-R in breast cancer is highlighted as imatinib, a specific PDGF-tyrosine kinase inhibitor, exerts an inhibitory effect on cancer cell proliferation, invasion and migration as well as HS-proteoglycans expression. Imatinib may be of a potential therapeutic usefulness in breast cancer regimes.
(Less)
- author
- Malavaki, Christina J. ; Roussidis, Andreas E. ; Gialeli, Chrisostomi LU ; Kletsas, Dimitris ; Tsegenidis, Theodore ; Theocharis, Achileas D. ; Tzanakakis, George N. and Karamanos, Nikos K.
- publishing date
- 2013-05
- type
- Contribution to journal
- publication status
- published
- keywords
- breast cancer, heparan sulfate proteoglycans, imatinib (Glivec®), invasion, migration, PDGF-R
- in
- FEBS Journal
- volume
- 280
- issue
- 10
- pages
- 2477 - 2489
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:23374223
- scopus:84877709417
- ISSN
- 1742-464X
- DOI
- 10.1111/febs.12163
- language
- English
- LU publication?
- no
- id
- b17601f1-5acc-4ff7-9728-376dcaa6a45f
- date added to LUP
- 2025-02-11 23:13:32
- date last changed
- 2025-03-12 00:49:28
@article{b17601f1-5acc-4ff7-9728-376dcaa6a45f,
abstract = {{<p>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. PDGF/PDGF-R-mediated signaling axis is highly associated with cancer progression. The regulatory role of PDGF-R in breast cancer is highlighted as imatinib, a specific PDGF-tyrosine kinase inhibitor, exerts an inhibitory effect on cancer cell proliferation, invasion and migration as well as HS-proteoglycans expression. Imatinib may be of a potential therapeutic usefulness in breast cancer regimes.</p>}},
author = {{Malavaki, Christina J. and Roussidis, Andreas E. and Gialeli, Chrisostomi and Kletsas, Dimitris and Tsegenidis, Theodore and Theocharis, Achileas D. and Tzanakakis, George N. and Karamanos, Nikos K.}},
issn = {{1742-464X}},
keywords = {{breast cancer; heparan sulfate proteoglycans; imatinib (Glivec®); invasion; migration; PDGF-R}},
language = {{eng}},
number = {{10}},
pages = {{2477--2489}},
publisher = {{John Wiley & Sons Inc.}},
series = {{FEBS Journal}},
title = {{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}},
url = {{http://dx.doi.org/10.1111/febs.12163}},
doi = {{10.1111/febs.12163}},
volume = {{280}},
year = {{2013}},
}