Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line.

Yi Wang,Jun‐Ichiro Ikeda,Yang Jiang,Tian Tian,Eiichi Morii,Hiroshi Ohtsu,Atsushi Sato

doi:10.1002/cam4.296

Yi Wang, Jun‐Ichiro Ikeda + Show 5 more

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https://doi.org/10.1002/cam4.296

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Abstract

Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine.

Highlights

Histamine, a biogenic amine, was first identified as an autacoid having potent vasoactive properties [1]
We previously demonstrated that Aldehyde dehydrogenase 1 (ALDH1) expression was correlated to size of tumor, lymphatic invasion, recurrence, and prognosis of patients in uterine endometrioid adenocarcinoma
The population of ALDH1 high cells was more invasive, antiapoptotic, and tumorigenic than the population of ALDH1 low cells in HEC-1 endometrioid adenocarcinoma cell line, in which abundant ALDH high cells were detected by Aldefluor assay as compared to other endometrioid adenocarcinoma cell lines [37]

Summary

Introduction

A biogenic amine, was first identified as an autacoid having potent vasoactive properties [1] It was recognized for its multiple regulatory activities in the immune systems [2,3,4]. Histamine is considered to play a critical role in cancer cell proliferation, migration, and invasion, the tumor microenvironment and immune system responses [5, 6, 12,13,14,15,16,17]. These various effects of histamine are mediated through the activation of specific histamine receptors (H1R, H2R, H3R, and H4R), which are all G protein-

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