Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy

Cordier, Dominik and Gerber, Alexander and Kluba, Christiane and Bauman, Andreas and Hutter, Gregor and Mindt, Thomas L. and Mariani, Luigi. (2014) Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy. Cancer Biotherapy and Radiopharmaceuticals, 29 (5). pp. 221-226.

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Official URL: https://edoc.unibas.ch/62333/

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In clinical trials, overexpression of neurokinin-1 receptors (NK1R) in gliomas has been exploited by intratumoral injection of its radiolabeled ligand, substance P (SP). However, despite proven NK1R expression, patients' response to the therapy was inhomogeneous. This study aims to identify the factors predicting response to NK1R-targeted glioma therapy, thereby allowing the discrimination between potential "responders" and "nonresponders" and thus a personalized therapeutic approach. Four widely used glioblastoma cell lines were examined concerning their RNA levels of full-length and truncated NK1R subtypes. Binding of SP to NK1R and internalization into glioma cells was studied by three different approaches using radiolabeled SP ((177)Lu-[DOTA, Thi(8), Met(O2)(11)]-SP), a fluorescence-labeled SP derivative (SP-FAM), and a toxin-SP conjugate (saporin-SP). While NK1R RNA was detected in all cases, receptor subtype analysis revealed impressive differences between the cell lines; LN319 exhibited the highest level of full-length NK1R RNA. Significant binding of SP conjugates to NK1R, cell internalization, and specific cell killing were only observed with the cell line LN319. Thus, different NK1R subtype profiles of glomerular basement membrane (GBM) cell lines appear to influence the binding of SP conjugates and their cell internalization properties. Both processes are crucial steps for NK1R-based targeted therapy. Pretherapeutic testing for NK1R subtype expression may therefore be advisable before initiation of this generally promising therapeutic modality.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Brain Tumor Biology (Mariani)
UniBasel Contributors:Mariani, Luigi
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Mary Ann Liebert
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Jul 2020 16:17
Deposited On:29 Jul 2020 16:17

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