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Effective Selection of a Well-Differentiated Type of Human Uterine Endometrial Carcinoma Cells by Transfection of the Sulfotransferase Gene and Possible Association of Sulfoglycolipids With Well-Differentiated Phenotypes
  1. Kyoko Tanaka, MD,
  2. Isamu Ishiwata, MD,
  3. Kaneyuki Kubushiro, MD,
  4. Mikio Mikami, MD,
  5. Daisuke Aoki, MD,
  6. Kazushige Kiguchi, MD and
  7. Masao Iwamori, PhD
  1. * Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo Japan;
  2. Ishiwata Gynecologic Hospital, Mito, Ibaraki, Japan;
  3. Ohashi Hospital, School of Medicine, Toho University, Tokyo, Japan;
  4. § Department of Obstetrics and Gynecology, School of Medicine, Tokai University, Isehara, Kanagawa, Japan;
  5. Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan; and
  6. # Faculty of Science and Technology, Kinki University, Osaka, Japan.
  1. Address correspondence and reprint requests to Kyoko Tanaka, MD, Keio University School of Medicine, Tokyo, Japan. E-mail: kkyokokeio{at}a5.keio.jp.

Abstract

Objectives Sulfatide has been shown to be characteristically increased on the apical surface of the normal endometrium at the secretory phase, and to be related with the formation of the glandular structure and the secretion of mucin from glands for the implantation of a fertilized egg. Additionally, sulfatides are expressed in the well-differentiated type, but not in the poorly differentiated type, of endometrial carcinomas. This suggests that sulfatides are a molecular marker of differentiated phenotypes. To further elucidate the biological significance of sulfoglycolipids, we transfected the sulfotransferase gene into endometrial carcinoma–derived cells without sulfoglycolipids and compared their glycolipid compositions and phenotypes with those of the original cells.

Materials and Methods The glycolipid sulfotransferase gene was transfected into endometrial carcinoma–derived SNG-II cells, the resultant transfected cells being found to frequently form a domelike structure, and some of them were selected as SNG-II-GST cells. We compared the glycolipid compositions and phenotypes of SNG-II and SNG-II-GST cells.

Results Although the original SNG-II cells grew in a paving stone pattern, SNG-II-GST cells formed a domelike structure. SNG-II-GST cells exhibited high GST activity and contained sulfoglycolipids, II3SO3-LacCer and II3SO3-Gg3Cer, which were not found in SNG-II cells. The amounts of sulfoglycolipids in SNG-II-GST cells were 1.5 times higher than those of gangliosides, and the proportions of LacCer and GM3 in SNG-II-GST cells were greatly different from those in SNG-II cells. SNG-II and SNG-II GST cells exhibited poorly differentiated and well-differentiated phenotypes on histochemical examination of cancerous nodules in nude mice. However, by means of an oxygen electrode, SNG-II-GST cells were found to be more resistant to anticancer drugs than SNG-II cells.

Conclusion Enhanced expression of sulfoglycolipids in poorly differentiated cells is a feasible means of selecting well-differentiated ones, and sulfoglycolipids are involved in the well-differentiated phenotype like those in the normal endometrium at the secretory phase.

  • Sulfoglycolipid
  • Ganglioside
  • Sulfotransferase
  • Differentiation
  • Anticancer drug

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Footnotes

  • The authors declare no conflicts of interest.

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