Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity
| Autor: | Haiyan Jia, David L. Selwood, Azadeh Bagherzadeh, Lili Cheng, Michelle Tickner, Ian Zachary |
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| Rok vydání: | 2010 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research medicine.medical_specialty Paclitaxel Cell Survival integrin Angiogenesis Integrin Antineoplastic Agents Biology migration Extracellular matrix chemistry.chemical_compound DU145 Cell Movement Cell Line Tumor Internal medicine Neuropilin 1 Cell Adhesion medicine Humans EG3287 Cell adhesion molecule Drug Synergism Cell migration VEGF Neuropilin-1 Peptide Fragments Fibronectins Vascular endothelial growth factor chemosensitivity Endocrinology Oncology chemistry Cancer research biology.protein Translational Therapeutics |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6605539 |
| Popis: | Background: Neuropilin-1 (NRP1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) recently implicated in tumour functions. Methods: In this study we used a specific antagonist of VEGF binding to the NRP1 b1 domain, EG3287, to investigate the functional roles of NRP1 in human carcinoma cell lines, non-small-cell lung A549, kidney ACHN, and prostate DU145 cells expressing NRP1, and the underlying mechanisms involved. Results: EG3287 potently displaced the specific binding of VEGF to NRP1 in carcinoma cell lines and significantly inhibited the migration of A549 and ACHN cells. Neuropilin-1 downregulation by siRNA also decreased cell migration. EG3287 reduced the adhesion of A549 and ACHN cells to extracellular matrix (ECM), and enhanced the anti-adhesive effects of a β1-integrin function-blocking antibody. EG3287 increased the cytotoxic effects of the chemotherapeutic agents 5-FU, paclitaxel, or cisplatin on A549 and DU145 cells, through inhibition of integrin-dependent cell interaction with the ECM. Conclusions: These findings indicate that NRP1 is important for tumour cell migration and adhesion, and that NRP1 antagonism enhances chemosensitivity, at least in part, by interfering with integrin-dependent survival pathways. A major implication of this study is that therapeutic strategies targeting NRP1 in tumour cells may be particularly useful in combination with other drugs for combating tumour survival, growth, and metastatic spread independently of an antiangiogenic effect of blocking NRP1. |
| Databáze: | OpenAIRE |
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