Possibility of Targeting Claudin-2 in Therapy for Human Endometrioid Endometrial Carcinoma
- PDF / 9,657,151 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 14 Downloads / 174 Views
GYNECOLOGIC ONCOLOGY: ORIGINAL ARTICLE
Possibility of Targeting Claudin-2 in Therapy for Human Endometrioid Endometrial Carcinoma Tadahi Okada 1,2 & Takumi Konno 1 & Takayuki Kohno 1 & Hiroshi Shimada 2 & Kimihito Saito 1,2 & Seiro Satohisa 2 & Tsuyoshi Saito 2 & Takashi Kojima 1 Received: 18 February 2020 / Revised: 24 May 2020 / Accepted: 2 June 2020 # Society for Reproductive Investigation 2020
Abstract Claudin-2 (CLDN-2) is a leaky-type tight junction protein, and its overexpression increases tumorigenesis of some types of cancer cells. In the present study, to examine the possibility of targeting CLDN-2 in the therapy for endometrioid endometrial adenocarcinoma, we investigated the regulation and role of CLDN-2 in endometriosis and endometrioid endometrial adenocarcinoma. In endometrioid endometrial adenocarcinoma tissues, marked upregulation of CLDN-2 was observed together with malignancy, while in endometriosis tissues, a change in the localization of CLDN-2 was observed. In cells of the endometrial adenocarcinoma cell line Sawano, which highly express CLDN-2, downregulation of CLDN-2 induced by the siRNA upregulated the epithelial barrier and inhibited cell migration. Furthermore, the downregulation of CLDN-2 affected the cell cycle and inhibited cell proliferation. In Sawano cells cultured with high-glucose medium, CLDN-2 expression was downregulated at the mRNA and protein levels. The high-glucose medium upregulated the epithelial barrier, cell proliferation, and migration, and inhibited cell invasion. The histone deacetylase (HDAC) inhibitor tricostatin A (TSA), which has antitumor effects, downregulated CLDN-2 expression, cell proliferation, invasion, and migration, and upregulated the epithelial barrier. The mitochondrial respiration level, an indicator of cancer metabolism, was downregulated by CLDN-2 knockdown and upregulated by the highglucose condition. Taken together, these results indicated that overexpression of CLDN-2 closely contributed to the malignancy of endometrioid endometrial adenocarcinoma. Downregulation of CLDN-2 via the changes of the glucose concentration and treatment with HDAC inhibitors may be important in the therapy for endometrial cancer. Keywords Claudin-2 . Malignancy . Human endometrioid endometrial carcinoma . High glucose . HDAC inhibitor . Cancer metabolism
Introduction Endometrial cancer was the sixth most commonly diagnosed cancer and the 14th leading cause of cancer death in women Tadahi Okada and Takumi Konno are equal first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00230-6) contains supplementary material, which is available to authorized users. * Takashi Kojima [email protected] 1
Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan
2
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan
worldwide in 2012 [1]. Its incidenc
Data Loading...
