Establishment and characterization of a primary and a metastatic melanoma cell line from Grey horses

• Published in: In vitro cellular & developmental biology. Animal 2014, Vol.50 (1), p.56-65
• Main Authors: Seltenhammer, Monika H, Sundström, Elisabeth, Meisslitzer-Ruppitsch, Claudia, Cejka, Petra, Kosiuk, Jedrzej, Neumüller, Josef, Almeder, Marlene, Majdic, Otto, Steinberger, Peter, Losert, Udo M, Stöckl, Johannes, Andersson, Leif, Sölkner, Johann, Vetterlein, Monika, Golovko, Anna
• Format: Article
• Language: English
• Subjects: Animal Genetics and Genomics; Animals; antigens; Biomedical and Life Sciences; CELL AND TISSUE MODELS; Cell Biology; Cell Culture; Cell culture techniques; Cell growth; Cell Line, Tumor; Cell lines; Cell Proliferation; chromosome number; Chromosomes; Chromosomes, Mammalian; Cultured cells; Developmental Biology; Genetic mutation; Genetics and Breeding; Genetik och förädling; Grey horse; Horses; humans; In vitro model; Karyotype; karyotyping; Life Sciences; Melanoma; Melanoma - genetics; Melanoma - pathology; Melanoma - veterinary; metastasis; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; pathogenesis; phenotype; Primary and metastatic melanoma; Stem Cells; Tumor cell line; Tumor suppressor; Tumors
• ISSN: 1071-2690; 1543-706X; 1543-706X
• DOI: 10.1007/s11626-013-9678-1

The Grey horse phenotype, caused by a 4.6 kb duplication in Syntaxin 17, is strongly associated with high incidence of melanoma. In contrast to most human melanomas with an early onset of metastasis, the Grey horse melanomas have an extended period of benign growth, after which 50% or more eventually undergo progression and may metastasize. In efforts to define changes occurring during Grey horse melanoma progression, we established an in vitro model comprised of two cell lines, HoMel-L1 and HoMel-A1, representing a primary and a metastatic stage of the melanoma, respectively. The cell lines were examined for their growth and morphological characteristics, in vitro and in vivo oncogenic potential, chromosome numbers, and expression of melanocytic antigens and tumor suppressors. Both cell lines exhibited malignant characteristics; however, the metastatic HoMel-A1 showed a more aggressive phenotype characterized by higher proliferation rates, invasiveness, and a stronger tumorigenic potential both in vitro and in vivo. HoMel-A1 displayed a near-haploid karyotype, whereas HoMel-L1 was near-diploid. The cell lines expressed melanocytic lineage markers such as TYR, TRP1, MITF, PMEL, ASIP, MC1R, POMC, and KIT. The tumor suppressor p53 was strongly expressed in both cell lines, while the tumor suppressors p16 and PTEN were absent in HoMel-A1, potentially implicating significance of these pathways in the melanoma progression. This in vitro model system will not only aid in understanding of the Grey horse melanoma pathogenesis, but also in unraveling the steps during melanoma progression in general as well as being an invaluable tool for development of new therapeutic strategies.