Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin

Hiroshi Uchida, Tetsuo Maruyama, Masanori Ono, Kuniaki Ohta, Takashi Kajitani, Hirotaka Masuda, Takashi Nagashima, Toru Arase, Hironori Asada, Yasunori Yoshimura

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Histone deacetylase inhibitors (HDACIs) have recently emerged as promising anticancer drugs to induce cell cycle arrest, cytodifferentiation, and apoptosis. It is suggested, however, that HDACIs promote cell migration and invasion depending on the cell type. We have reported previously that treatment with HDACIs, including trichostatin A and suberoylanilide hydroxamic acid (SAHA) or progesterone in combination with estrogen, can induce cytodifferentiation of endometrial adenocarcinoma Ishikawa cells through upregulation of glycodelin, a progesterone-induced endometrial glycoprotein. Given the reported role of glycodelin in cell motility and the migration-modulating potential of HDACIs, we investigated using wound healing assay and transwell migration assay whether ovarian steroid hormones, trichostatin A, or SAHA affects cell migration in endometrial cancer cell lines, Ishikawa and RL95-2. Treatment with ovarian steroid hormones, trichostatin A, and SAHA enhanced cell migration together with up-regulation of glycodelin. SAHA-augmented cell migration was almost completely blocked by gene silencing of glycodelin. Furthermore, overexpression of gycodelin alone resulted in increased cell motility in Ishikawa cells. Our results collectively indicate that glycodelin positively regulates cell motility acting as a mediator of HDACI-enhanced endometrial cell migration, suggesting the involvement of glycodelin in the dynamic endometrial gland morphogenesis during menstrual cycle. Our results raise a possibility that the use of HDACIs in the therapy for glycodelin-inducible endometrial and presumably other gynecological cancers may enhance invasion in cases in which the HDACIs fail to exert differentiation-inducing and/or antiproliferative effects.

Original languageEnglish
Pages (from-to)896-902
Number of pages7
JournalEndocrinology
Volume148
Issue number2
DOIs
Publication statusPublished - 2007 Feb

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Histone Deacetylase Inhibitors
Cell Movement
Adenocarcinoma
Up-Regulation
trichostatin A
Progesterone
Steroids
Hormones
Glycodelin
Gene Silencing
Endometrial Neoplasms
Menstrual Cycle
Cell Cycle Checkpoints
Morphogenesis
Wound Healing
Glycoproteins
Estrogens
Apoptosis
Cell Line
vorinostat

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin. / Uchida, Hiroshi; Maruyama, Tetsuo; Ono, Masanori; Ohta, Kuniaki; Kajitani, Takashi; Masuda, Hirotaka; Nagashima, Takashi; Arase, Toru; Asada, Hironori; Yoshimura, Yasunori.

In: Endocrinology, Vol. 148, No. 2, 02.2007, p. 896-902.

Research output: Contribution to journalArticle

Uchida, Hiroshi ; Maruyama, Tetsuo ; Ono, Masanori ; Ohta, Kuniaki ; Kajitani, Takashi ; Masuda, Hirotaka ; Nagashima, Takashi ; Arase, Toru ; Asada, Hironori ; Yoshimura, Yasunori. / Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin. In: Endocrinology. 2007 ; Vol. 148, No. 2. pp. 896-902.
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