A cloned human germ cell tumor‐derived cell line differentiating in culture

• Published in: International journal of cancer Vol. 77; no. 5; pp. 710 - 719
• Main Authors: Tienari, Jukka, Reima, Ilkka, Larramendy, Marcelo L., Knuutila, Sakari, von Boguslawsky, Kristina, Kaartinen, Matti, Virtanen, Ismo, Lehtonen, Eero
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 31.08.1998; Wiley-Liss
• Subjects: Animals; Biological and medical sciences; Cell Culture Techniques - methods; Cell Differentiation - drug effects; Chromosome Aberrations; Clone Cells; Desmin - analysis; General aspects (metabolism, cell proliferation, established cell line...); Germinoma - genetics; Germinoma - pathology; Humans; Immunohistochemistry; Immunosuppression; Keratins - analysis; Lymphatic Metastasis; Male; Medical sciences; Mesoderm - cytology; Mesoderm - drug effects; Phenotype; Rats; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology; Transplantation, Heterologous; Tretinoin - pharmacology; Tumor cell; Tumor Cells, Cultured; Tumors; Vimentin - analysis; Human; Biological marker; Tumorigenicity; Malignant tumor; Cell differentiation; Testicle; Cell line establishment; In vitro; Characterization; Germ cell tumor; Pathology; Histopathology; Ultrastructure; Cytogenetics; Genetics; Male genital diseases; Testicular diseases; Karyotype
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19980831)77:5<710::AID-IJC9>3.0.CO;2-Y

We have derived a clonal cell line (HGCT‐1) from a lymph node metastasis of a primary testicular germ cell tumor (GCT). The tumor was negative for the embryonal carcinoma (EC) cell marker BerH2 but positive for vimentin, cytokeratin (CK) and desmin. Comparative genomic hybridization (CGH) revealed a high‐level amplification at 12p that was observed in both the metastatic tumor and in the cultured HGCT‐1 cells. In vitro, the phenotype of HGCT‐1 cells was modulated by the culture conditions. In the presence of 10% fetal calf serum (FCS), the majority of HGCT‐1 cells lacked CK and desmin. If cultured in 0.5% FCS, HGCT‐1 cells acquired a uniform co‐expression of vimentin, CK and desmin. Upon treatment with retinoic acid (RA), HGCT‐1 cells lost the expression of desmin, but exhibited abundant CK filaments. Simultaneously, they started to express desmoplakin, form desmosomes and flatten on the culture substratum. The RA‐induced changes were irreversible, whereas those following the culture in 0.5% FCS were at least partially reversible. When xenografted into an immunosuppressed rat, HGCT‐1 cells formed a tumor consisting of epithelial‐ and mesenchymal‐like structures. HGCT‐1 cells thus represent a pluripotential cell system with a capacity for reversible phenotypic modulation and for irreversible differentiation into epithelial‐type cells. The behavior of this novel cell line, distinct from established EC cell models, suggests a complex regulation of GCT cell differentiation. Int. J. Cancer 77:710–719, 1998. © 1998 Wiley‐Liss, Inc.