Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

Junfeng Zhao,Xiaozhou Bao,Jie Lin,Haochuan Zhang,Wenqiang Lu,Xiangdong Wang,Jinhui Shen,Xiaoming Chen,Le Qin,Hua Zhang,Congde Chen,Xiaokun Lin

doi:10.1186/1479-5876-10-46

Abstract

The testicular yolk sac tumor (TYST) is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

Highlights

The testicular yolk sac tumor (TYST) is the most common neoplasm originated from germ cells differentiated abnormally [1], while germ cell tumors in the testis account for approximately 60-75% of pediatric malignant testicular tumors
Testicular germ cell tumors account for over 95% of all testicular neoplasms and the incidence was doubled worldwide over past decades up to 7.5/100,000 [13], while pediatric germ cell tumors account for 60-75% of pediatric testicular tumors [14], mostly as yolk sac tumor
The current study established the TYST model by the passage from the primary TYST cells to the 7th generation in total 95 nude mice during 15 months

Summary

Introduction

The testicular yolk sac tumor (TYST) is the most common neoplasm originated from germ cells differentiated abnormally [1], while germ cell tumors in the testis account for approximately 60-75% of pediatric malignant testicular tumors. The TYST is still a highly malignant neoplasm with poor prognosis, increased resistance to chemotherapy, recurrence after initial chemotherapy or surgery, and the side effects of chemotherapeutics, even though the. The present studies aimed at establishing the animal model of TYST and the human TYST cell line and evaluating the characteristics of the disease and bio-function of human TYST cells. The present study evaluated the role of ATRA as an inducer of differentiation in a variety of tumor cells in the growth TYST cell lines in vitro and explored the molecular mechanism of TYST cell proliferation. Effects of cisplatin on TYST cell apoptosis and the expression of P53 and Bcl-2 genes were investigated

Methods

Results

Conclusion