Therapeutic potential of SOX2 inhibition for embryonal carcinoma

J Urol. 2012 May;187(5):1876-81. doi: 10.1016/j.juro.2011.12.058. Epub 2012 Mar 16.

Abstract

Purpose: Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model.

Materials and methods: SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model.

Results: In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo.

Conclusions: This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Embryonal / metabolism*
  • Carcinoma, Embryonal / pathology
  • Carcinoma, Embryonal / therapy*
  • Cell Death
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Silencing
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred Strains
  • RNA, Small Interfering / therapeutic use
  • SOXB1 Transcription Factors / antagonists & inhibitors*
  • SOXB1 Transcription Factors / metabolism*
  • Seminoma / metabolism
  • Seminoma / pathology
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / therapy*
  • Transfection

Substances

  • RNA, Small Interfering
  • SOX2 protein, human
  • SOXB1 Transcription Factors