视黄醇脱氢酶 10 促进卵巢透明细胞癌的肿瘤干性和细胞内碳水化合物储存。

Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas.

机构信息

Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.

出版信息

Cancer Biomark. 2022;34(4):673-679. doi: 10.3233/CBM-210435.

DOI:10.3233/CBM-210435

PMID:35634847

Abstract

BACKGROUND

Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed.

OBJECTIVE

The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs.

METHODS

Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression.

RESULTS

Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells.

CONCLUSIONS

In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.

摘要

背景

卵巢透明细胞癌（OCCC）在现有治疗方法中经常复发且难以治疗，因此急需新的治疗方法。

目的

本研究旨在积累概念验证，以检查 RDH10 作为治疗 OCCC 的治疗靶点的可行性。

方法

通过免疫组织化学方法，在 111 例原发性上皮性卵巢癌中评估 RDH10 的表达情况，其中包括 55 例 OCCC、31 例卵巢子宫内膜样癌和 25 例卵巢浆液性癌。在 OCCC 细胞中评估 RDH10 引起的球形生成能力。为了分析 RDH10 是否通过维生素 A-糖异生途径促进碳水化合物储存，我们测量了磷酸烯醇丙酮酸羧激酶 1（PCK1）蛋白水平和细胞内碳水化合物含量，以响应修饰的 RDH10 表达。