tretinoin and Endodermal-Sinus-Tumor

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.

Topics: alpha-Fetoproteins; Animals; Cell Cycle; Cell Proliferation; Child, Preschool; Cisplatin; Clone Cells; Endodermal Sinus Tumor; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Testicular Neoplasms; Tretinoin; Tumor Burden; Xenograft Model Antitumor Assays

Retinoic acid treatment of the multipotent human embryonal carcinoma cell line GCT 27 X-1 induced differentiation into an epithelial cell type which morphologically resembled rodent visceral endoderm in vitro. The differentiated cells expressed some markers characteristic of yolk sac, such as cytokeratin 19 and extracellular matrix proteins, but none of the secreted serum proteins produced by normal yolk sac or liver. HNF-3 alpha expression increased upon retinoic acid-induced GCT 27 X-1 differentiation. This increase in HNF-3 alpha expression may characterize an early stage in the differentiation of extraembryonic endoderm. In support of this hypothesis, we found that a yolk sac carcinoma cell line with a phenotype similar to rodent visceral endoderm expressed transcripts for HNF-1 alpha, -1 beta, -3 alpha, -3 beta, -3 gamma, and 4, whereas yolk sac carcinoma cell lines resembling rodent parietal endoderm expressed transcripts for HNF-3 alpha. The results support the conclusion that hepatocytic transcription factors, particularly HNF-3 alpha, may play an important role in early endodermal differentiation in man.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antibody Specificity; Antigens, Surface; Biomarkers; Blotting, Northern; Carbohydrate Sequence; Carcinoma, Embryonal; Carcinoma, Hepatocellular; Cell Differentiation; Cell Line; Cytoskeletal Proteins; DNA-Binding Proteins; Endoderm; Endodermal Sinus Tumor; Extracellular Matrix Proteins; Fluorescent Antibody Technique; Gene Expression; Hepatocyte Nuclear Factor 3-alpha; Humans; Kinetics; Laminin; Liver Neoplasms; Models, Biological; Molecular Sequence Data; Nuclear Proteins; Restriction Mapping; RNA, Messenger; Rodentia; Transcription Factors; Transcription, Genetic; Tretinoin; Tumor Cells, Cultured