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Erschienen in: Journal of Cancer Research and Clinical Oncology 9/2020

02.06.2020 | Original Article – Cancer Research

Cholecystokinin type 2 receptor in colorectal cancer: diagnostic and therapeutic target

verfasst von: Jiang Chang, Zeng-Shan Liu, De-Feng Song, Meng Li, Song Zhang, Ke Zhao, Yu-Ting Guan, Hong-Lin Ren, Yan-Song Li, Yu Zhou, Xi-Lin Liu, Shi-Ying Lu, Pan Hu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2020

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Abstract

Introduction

Cholecystokinin type 2 receptor (CCK2R), which mediates the action of gastrin and cholecystokinin (CCK), has been demonstrated to promote the proliferation of colorectal cancer (CRC). A number of studies showed that CCK2R overexpressed in gastric cancer and pancreatic cancer but few in CRC. The correlation between CCK2R expression and clinicopathological characteristics is also not clear.

Methods

This study investigated CCK2R expression in a wide range of cell lines and clinical CRC samples, and explored expression pattern and prognostic value of CCK2R in relation to clinicopathological parameters. The location and expression levels of CCK2R were measured by immunocytochemical (ICC), qRT-PCR and Western blot. The druggability and antineoplastic effects of CCK2R as a therapeutic target were investigated using an anti-CCK2R targeting recombinant toxin named rCCK8PE38 by CCK-8 assay.

Results

Compared with paracarcinoma tissues, tumor samples showed overexpression of CCK2R (p = 0.028) including both CRC tissue and plasma samples, with plasma detection showing a significant indication for CCK2R evaluation. Aberrant expression correlated significantly with histological type (p = 0.032) and p53 status (p < 0.01), and patients with CCK2R overexpression had significantly lower disease-free survival. Application of rCCK8PE38 demonstrated the specificity and druggability of CCK2R as a therapeutic target, providing a strategy for clinical case screening of drugs targeting CCK2R.

Conclusion

This study highlighted the aberrant expression and clinical correlation of CCK2R and reveals its diagnostic, prognostic and treatment value in CRC. We hypothesize that CCK2R serve as a target for the diagnosis and treatment of this cancer.
Literatur
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Zurück zum Zitat Hellmich MR, Rui XL, Hellmich HL, Fleming RY, Evers BM, Townsend CM Jr (2000) Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem 275:32122–32128CrossRef Hellmich MR, Rui XL, Hellmich HL, Fleming RY, Evers BM, Townsend CM Jr (2000) Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem 275:32122–32128CrossRef
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Metadaten
Titel
Cholecystokinin type 2 receptor in colorectal cancer: diagnostic and therapeutic target
verfasst von
Jiang Chang
Zeng-Shan Liu
De-Feng Song
Meng Li
Song Zhang
Ke Zhao
Yu-Ting Guan
Hong-Lin Ren
Yan-Song Li
Yu Zhou
Xi-Lin Liu
Shi-Ying Lu
Pan Hu
Publikationsdatum
02.06.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03273-z

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