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Kolorz, J.* ; Demir, S.* ; Gottschlich, A.* ; Beirith, I.* ; Ilmer, M.* ; Lüthy, D.* ; Walz, C.* ; Dorostkar, M.M.* ; Magg, T.* ; Hauck, F.* ; von Schweinitz, D.* ; Kobold, S. ; Kappler, R.* ; Berger, M.*

The neurokinin-1 receptor is a target in pediatric rhabdoid tumors.

Curr. Oncol. 29, 94-110 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apoptosis ; Cancer ; Nk-1 Receptor ; Nk-1 Receptor Antagonist ; Rhabdoid Tumor ; Substance P; Atypical Teratoid/rhabdoid Tumors; Substance-p; Childhood Neuroblastoma; Nk-1 Receptor; Hepatoblastoma; Antagonists; Biology; Cells; Smarcb1/ini1; Chemotherapy
ISSN (print) / ISBN 1198-0052
e-ISSN 1718-7729
Zeitschrift Current Oncology
Quellenangaben Band: 29, Heft: 1, Seiten: 94-110 Artikelnummer: , Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Unit for Clinical Pharmacology (KKG-EKLiP)
Förderungen Promotionsstudium Förderung für Forschung und Lehre" program from the University of Mu-nich, LMU