Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Establishment of a versatile seminoma model indicates cellular plasticity of germ cell tumor cells

Establishment of a versatile seminoma model indicates cellular plasticity of germ cell tumor cells In western countries, 60% of all malignancies diagnosed in men between 17–45 years of age are germ cell tumors (GCT). GCT arise from the common precursor lesion carcinoma in situ, which transforms within an average of 9 years into invasive Type‐II GCTs. Seminomas are considered to be the default developmental pathway of carcinoma in situ cells and the seminoma‐like cell line TCam‐2 has been used to study seminoma biology in vitro. However, the generation of an animal model, which would allow for the in vivo analysis of seminoma formation, remained elusive. We applied transplantation approaches using TCam‐2 cell transfer into ectopic (skin, brain) and orthopic (testis) sites of immunodeficient mice. We demonstrate that a transplantation into the seminiferous tubules results in formation of a carcinoma in situ/seminoma. In contrast, TCam‐2 cells adopt an embryonal carcinoma‐like fate when grafted to the flank or corpus striatum and display downregulation of the seminoma marker SOX17 and upregulation of the embryonal carcinoma markers SOX2 and CD30. Grafted TCam‐2 cells reduce AKT‐, ERK‐, EphA3‐, and Tie2/TEK‐signaling to levels comparable to embryonal carcinoma cells. Hence, TCam‐2 cell transplantation into the testis generated a carcinoma in situ/seminoma mouse model, which enables addressing the biology of these tumors in vivo. The fact that TCam‐2 cells give rise to a carcinoma in situ/seminoma or embryonal carcinoma in a transplantation site specific manner implies that conversion of carcinoma in situ/seminoma to an embryonal carcinoma does not require additional genetic aberrations but relies on signals from the tumor‐microenvironment. © 2012 Wiley Periodicals, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genes, Chromosomes and Cancer Wiley

Establishment of a versatile seminoma model indicates cellular plasticity of germ cell tumor cells

Download PDF
10 pages

Loading next page...
 
/lp/wiley/establishment-of-a-versatile-seminoma-model-indicates-cellular-IIYmmPuYUW

References (28)

Publisher
Wiley
Copyright
Copyright © 2012 Wiley Periodicals, Inc.
ISSN
1045-2257
eISSN
1098-2264
DOI
10.1002/gcc.21958
pmid
22489004
Publisher site
See Article on Publisher Site

Abstract

In western countries, 60% of all malignancies diagnosed in men between 17–45 years of age are germ cell tumors (GCT). GCT arise from the common precursor lesion carcinoma in situ, which transforms within an average of 9 years into invasive Type‐II GCTs. Seminomas are considered to be the default developmental pathway of carcinoma in situ cells and the seminoma‐like cell line TCam‐2 has been used to study seminoma biology in vitro. However, the generation of an animal model, which would allow for the in vivo analysis of seminoma formation, remained elusive. We applied transplantation approaches using TCam‐2 cell transfer into ectopic (skin, brain) and orthopic (testis) sites of immunodeficient mice. We demonstrate that a transplantation into the seminiferous tubules results in formation of a carcinoma in situ/seminoma. In contrast, TCam‐2 cells adopt an embryonal carcinoma‐like fate when grafted to the flank or corpus striatum and display downregulation of the seminoma marker SOX17 and upregulation of the embryonal carcinoma markers SOX2 and CD30. Grafted TCam‐2 cells reduce AKT‐, ERK‐, EphA3‐, and Tie2/TEK‐signaling to levels comparable to embryonal carcinoma cells. Hence, TCam‐2 cell transplantation into the testis generated a carcinoma in situ/seminoma mouse model, which enables addressing the biology of these tumors in vivo. The fact that TCam‐2 cells give rise to a carcinoma in situ/seminoma or embryonal carcinoma in a transplantation site specific manner implies that conversion of carcinoma in situ/seminoma to an embryonal carcinoma does not require additional genetic aberrations but relies on signals from the tumor‐microenvironment. © 2012 Wiley Periodicals, Inc.

Journal

Genes, Chromosomes and Cancer – Wiley

Published: Jul 1, 2012

There are no references for this article.