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

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

Description

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.

Sujets

• Human
• Clone
• Model
• Atra
• Cisplatin

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 11
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Zhao et al . Journal of Translational Medicine 2012, 10 :46 http://www.translational-medicine.com/content/10/1/46

R E S E A R C H Open Access Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor Junfeng Zhao 1 , Congde Chen 1 , Haochuan Zhang 1 , Jinhui Shen 1 , Hua Zhang 1 , Xiaokun Lin 1 , Le Qin 1 , Xiaozhou Bao 1 , Jie Lin 1 , Wenqiang Lu 1 , Xiangdong Wang 2 and Xiaoming Chen 1,2,3*

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. Keywords: Testicular yolk sac tumor, Human, Clone, Model, ATRA, Cisplatin

Introduction survival rate of patients with TYST was improved after The testicular yolk sac tumor (TYST) is the most com-  surgical resection or platinum-based combination che- mon neoplasm originated from germ cells differentiated  motherapy, e.g. cisplatin, etoposide and bleomycin [3]. abnormally [1], while germ cell tumors in the testis The regulation of cell differentiation from immature account for approximately 60-75% of pediatric malig-  malignant tumor cells to mature was suggested as a nant testicular tumors. The yolk sac tumor as endoder- potential therapy for tumor s [4]. Conventional radio- mal sinus tumor is a common malignant tumor therapy and/or chemotherapy were found to suppress accounting for 1-2% of cancers in men and one of the  the bone marrow and immune function through influen- most common types of cancer in young men between cing cell phenotypes [5]. The cell apoptosis is closely 15-35 ages. Of them, the TYST mainly occurs in neo-  related with the tumorigene ss, tumor development and nates and infants, different from adolescences or adults  insensitivity of chemotherapy/radiation therapy [6]. who composed of multiple germ cells and having own There are limited studies on human TYSTs, although biological characters [2]. YST has been studies in cells from male murine embry- The TYST is still a highly malignant neoplasm with  onal carcinoma in vitro [7] and ovarian YST cell lines poor prognosis, increased resistance to chemotherapy, [8]. The present studies aimed at establishing the animal recurrence after initial chemotherapy or surgery, and  model of TYST and the human TYST cell line and eval- the side effects of chemother apeutics, even though the uating the characteristics of the disease and bio-function of human TYST cells. The present study evaluated the * Correspondence: [e-mail] role of ATRA as an inducer of differentiation in a vari- 1 Department of Pediatric Surgery, the Second Hospital, Wenzhou Medical ety of tumor cells in the growth TYST cell lines in vitro C Fu o l l l le li g st e, of We au n t z h h o o r u i , nf C o h r in m a ationisavailableattheendofthearticle and explored the molecular mechanism of TYST cell © 2012 Zhao et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.