Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo

Tomokazu Umezu, Kiyosumi Shibata, Maiko Shimaoka, Hiroaki Kajiyama, Eiko Yamamoto, Kazuhiko Ino, Akihiro Nawa, Takeshi Senga, Fumitaka Kikkawa

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11 Citations (Scopus)

Abstract

Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is bound to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, and glypicans can regulate the activity of a wide variety of growth and survival factors. We report here that GPC3 was expressed in clear cell carcinoma of the ovary, and not in other carcinomas. To evaluate the phenotype and potential preclinical relevance, we generated an ovarian cancer cell line stably transfected with plasmids encompassing shRNA targeting GPC3. We show that the clear cell carcinoma cell line with silenced GPC3 expression (GPC3 [-]) was more sensitive to paclitaxel than GPC3 (+) cells. In addition, the GPC3 silencing induced sensitization to paclitaxel was associated with the activation of an apoptosis pathway, as shown by flow cytometry. Moreover, we investigated the effect of GPC3 on peritoneal metastases using nude mice. Peritoneal metastases caused by GPC3 (-) were more sensitive to paclitaxel than those caused by GPC3 (+) cells. These results indicate that increased GPC3 expression in a clear cell carcinoma cell line may play a protective role against apoptosis, and so the downregulation of GPC3 may be a potential target to increase sensitivity to paclitaxel-induced apoptosis in clear cell carcinoma.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalCancer science
Volume101
Issue number1
DOIs
Publication statusPublished - 01-01-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Umezu, T., Shibata, K., Shimaoka, M., Kajiyama, H., Yamamoto, E., Ino, K., Nawa, A., Senga, T., & Kikkawa, F. (2010). Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo. Cancer science, 101(1), 143-148. https://doi.org/10.1111/j.1349-7006.2009.01382.x