Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression

Summary Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we inv...

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Published in:Pigment cell and melanoma research Vol. 24; no. 3; pp. 490 - 503
Main Authors: Soo, Julia K., MacKenzie Ross, Alastair D., Kallenberg, David M., Milagre, Carla, Heung Chong, W., Chow, Jade, Hill, Lucy, Hoare, Stacey, Collinson, Rebecca S., Hossain, Mehnaz, Keith, W. Nicol, Marais, Richard, Bennett, Dorothy C.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01-06-2011
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Summary:Summary Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β‐galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth‐phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event.
Bibliography:istex:D0C79D53054CD5C3C3FF0C02E99EC849503B4DC6
ArticleID:PCMR850
ark:/67375/WNG-5XSRQVCT-V
Current address: Department of Plastic Surgery, St. Thomas’s Hospital, London, UK.
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ISSN:1755-1471
1755-148X
DOI:10.1111/j.1755-148X.2011.00850.x