Next Article in Journal
Potent Anticancer Effect of the Natural Steroidal Saponin Gracillin Is Produced by Inhibiting Glycolysis and Oxidative Phosphorylation-Mediated Bioenergetics
Previous Article in Journal
Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Cancers
Volume 12
Issue 4
10.3390/cancers12040912
cancers-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

Genetic Deficiency of the Histamine H4-Receptor Reduces Experimental Colorectal Carcinogenesis in Mice

by
Bastian Schirmer
1,†,
Tamina Rother
1,2,†,
Inga Bruesch
3,
Andre Bleich
3,
Christopher Werlein
4,
Danny Jonigk
4,
Roland Seifert
1 and
Detlef Neumann
1,*
1
Institute of Pharmacology, Hannover Medical School, 30625 Hannover, Germany
2
Institute of Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
3
Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany
4
Institute of Pathology and German Center of Lung Research (DZL), Partner site BREATH, Hannover Medical School, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
†
These authors equally contributed to this study.
Cancers 2020, 12(4), 912; https://doi.org/10.3390/cancers12040912
Received: 26 February 2020 / Revised: 5 April 2020 / Accepted: 6 April 2020 / Published: 8 April 2020
View Full-Text Download PDF
Browse Figures
Review Reports

Abstract

Colorectal cancer (CRC), a severe complication of inflammatory bowel diseases, is a common type of cancer and accounts for high mortality. CRC can be modeled in mice by application of the tumor promoter, azoxymethane (AOM), in combination with dextran sodium sulfate (DSS), which are able to induce colitis-like manifestations. Active colitis correlates with high mucosal concentrations of histamine, which, together with the histamine receptor subtype 4 (H4R), provide a pro-inflammatory function in a mouse colitis model. Here, we analyzed whether H4R is involved in the pathogenesis of AOM/DSS-induced CRC in mice. As compared to wild type (WT) mice, AOM/DSS-treated mice lacking H4R expression (TM) demonstrate ameliorated signs of CRC, i.e., significantly reduced loss of body weight, stiffer stool consistency, and less severe perianal bleeding. Importantly, numbers and diameters of tumors and the degree of colonic inflammation are dramatically reduced in TM mice as compared to WT mice. This is concomitant with a reduced colonic inflammatory response involving expression of cyclooxygenase 2 and the production of C-X-C motif chemokine ligand 1 (CXCL1) and CXCL2. We conclude that H4R is involved in the tumorigenesis of chemically-induced CRC in mice via cyclooxygenase 2 expression and, probably, CXCL1 and CXCL2 as effector molecules. View Full-Text
Keywords: histamine; H4 receptor; colorectal cancer; mouse model; cyclooxygenase 2 histamine; H4 receptor; colorectal cancer; mouse model; cyclooxygenase 2
►▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

SciFeed

Share and Cite

MDPI and ACS Style

Schirmer, B.; Rother, T.; Bruesch, I.; Bleich, A.; Werlein, C.; Jonigk, D.; Seifert, R.; Neumann, D. Genetic Deficiency of the Histamine H4-Receptor Reduces Experimental Colorectal Carcinogenesis in Mice. Cancers 2020, 12, 912. https://doi.org/10.3390/cancers12040912

AMA Style

Schirmer B, Rother T, Bruesch I, Bleich A, Werlein C, Jonigk D, Seifert R, Neumann D. Genetic Deficiency of the Histamine H4-Receptor Reduces Experimental Colorectal Carcinogenesis in Mice. Cancers. 2020; 12(4):912. https://doi.org/10.3390/cancers12040912

Chicago/Turabian Style

Schirmer, Bastian, Tamina Rother, Inga Bruesch, Andre Bleich, Christopher Werlein, Danny Jonigk, Roland Seifert, and Detlef Neumann. 2020. "Genetic Deficiency of the Histamine H4-Receptor Reduces Experimental Colorectal Carcinogenesis in Mice" Cancers 12, no. 4: 912. https://doi.org/10.3390/cancers12040912

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop