Expression of p57KIP2 reduces growth and invasion, and induces syncytialization in a human placental choriocarcinoma cell line, BeWo

Katsuhiko Takahashi; Yui Yoneyama; Naoya Koizumi; Naoki Utoguchi; Naohiro Kanayama; Nobuaki Higashi

doi:10.1016/j.placenta.2020.11.010

Expression of p57^KIP2 reduces growth and invasion, and induces syncytialization in a human placental choriocarcinoma cell line, BeWo

Placenta. 2021 Jan 15:104:168-178. doi: 10.1016/j.placenta.2020.11.010. Epub 2020 Dec 1.

Authors

Katsuhiko Takahashi¹, Yui Yoneyama², Naoya Koizumi³, Naoki Utoguchi⁴, Naohiro Kanayama⁵, Nobuaki Higashi⁶

Affiliations

¹ Department of Biochemistry, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan; Department of Anatomy, Showa Univerisity School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. Electronic address: ka-takahashi@hoshi.ac.jp.
² Department of Biochemistry, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. Electronic address: yui1308pigu@docomo.ne.jp.
³ Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo, 194-8543, Japan. Electronic address: koizumi@ac.shoyaku.ac.jp.
⁴ Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo, 194-8543, Japan. Electronic address: utoguchi@ac.shoyaku.ac.jp.
⁵ Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 3600, Handa-cho, Hamamatsu, Shizuoka, 431-3192, Japan. Electronic address: kanayama@shiz-med-sci.ac.jp.
⁶ Department of Biochemistry, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. Electronic address: n-higashi@hoshi.ac.jp.

PMID: 33360007
DOI: 10.1016/j.placenta.2020.11.010

Abstract

Introduction: Syncytiotrophoblasts are the major components of the human placenta involved in fetal maternal exchange and hormone secretion. The syncytiotrophoblasts arise from the fusion of villous cytotrophoblasts. The cell cycle suppressor p57^KIP2 is known to be an essential molecule for proper trophoblast differentiation during placental formation.

Methods: We generated p57^KIP2-expressing BeWo transfectant cells. Proliferation assay and matrigel invasion assay were used to characterize p57^KIP2-expressing BeWo transfectant cells. To reveal the role of p57^KIP2 in syncytialization, we proceeded syncytium formation analysis and qRT-PCR for detection of the expression levels Syncytin-1, Syncytin-2 and their receptors.

Results: The human choriocarcinoma cell line, BeWo has undetectable levels of p57^KIP2 expression. Expression of p57^KIP2 reduced cell proliferation rate and extracellular matrix invasion activity. p57^KIP2 expressing cells displayed multinucleated cells associated with syncytiotrophoblast differentiation. In the syncytialization event, p57^KIP2 was found to potentiate forskolin-induced upregulation of Syncytin-2 in a cAMP-independent manner.

Discussion: These results indicate that the expression of p57^KIP2 may act on the proliferation/invasion inhibitory factor and enhance the expression of Syncytin-2, which are associated with syncytialization in cytotrophoblasts.

Keywords: BeWo cell line; Syncytialization; Trophoblast; p57(KIP2).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / physiology
Cell Line, Tumor
Cell Proliferation / physiology*
Cyclin-Dependent Kinase Inhibitor p57 / genetics
Cyclin-Dependent Kinase Inhibitor p57 / metabolism*
Female
Humans
Placenta / metabolism*
Placenta / pathology
Pregnancy
Trophoblasts / metabolism*

Substances

Cyclin-Dependent Kinase Inhibitor p57