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. 2012 Mar 13:10:46.
doi: 10.1186/1479-5876-10-46.

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

Junfeng Zhao  1 , Congde Chen, Haochuan Zhang, Jinhui Shen, Hua Zhang, Xiaokun Lin, Le Qin, Xiaozhou Bao, Jie Lin, Wenqiang Lu, Xiangdong Wang, Xiaoming Chen
Affiliations

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

Junfeng Zhao et al. J Transl Med. .

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.

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Figures

Figure 1
Figure 1
Average volumes of tumor driven from the primary generation, the first generation and the second generation of testicular yolk sac tumor (TYST) cells were compared with the number of cell cycles (A). The tumor was formed from the generation four of TYST cells and on after the subcutaneous transplantation (B). Histogram of tumor formed from cloned TYST cells stained with HE (C, × 400). Ultrastructure of cloned TYST cells with basement membrane materials, oval and enlargement nuclei, and glandular-like structures between cells (D, × 5000).
Figure 2
Figure 2
Histogram of the expressions of alpha- fetoprotein (A), placental alkaline phosphatase (B) and cytokeratins (C) in the tissue formed from cloned testicular yolk sac tumor cells and stained by Immunohistochemistry. Chromosomes with the diploid structure in cloned testicular yolk sac tumor cells (D). The origin magnification was × 400.
Figure 3
Figure 3
Cloned cells of testicular yolk sac tumors adhered and grew in the bundle toward the certain direction arranged with multiple overlapping growths (A, × 100), obvious heteromorphism and different shapes in size with H&E staining (B, × 200). Microvilli were noted on the cell surface between cells (C, × 8000), with the irregular nuclear (D, × 10000).
Figure 4
Figure 4
Cloned testicular yolk sac tumor cell growth curve during 8 day culture (A), with some abnormal chromosomes (B, X400), or positive expression of alpha- fetoprotein (C, × 200), rather than beta-subunit human chorionic gonadotrophin (D, × 200).
Figure 5
Figure 5
Inhibitory effects of all-trans-retinoic acid (ATRA) at different concentrations on cell proliferation (A) measured by values of the optimal density (OD) for 24, 48 and 72 hours, or the expression of RAR-β mRNA during 24-72 hours after the treatment with ATPA at concentration of 10-6 M (B) and treated with different concentrations of ATRA at 48 hours (c).
Figure 6
Figure 6
All closed cells used for the measurement of cisplatin effects were alpha- fetoprotein -stained positive (A1). Apoptotic cells were detected with AO/EB staining (A2). Increased TUNEL-positive cells were detected 12 hours after the treatment with cisplatin (A4) or vehicle (A3). The expression of p53 and Bcl-2 proteins was altered 12 hours and on after the treatment with vehicle (B1 and B3) or cisplantin (B2 and B4), respectively. Values of optimal density of p53 (C) and Bcl-2 protein staining (D) were calculated during 12 and 72 hours after cisplatin treatment.
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