title: Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression.
abstract: 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.
authors.affiliation: Division of Biomedical Sciences, St. George's, University of London, UK.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Soo
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Mackenzie Ross
authors.forename: David M
authors.initials: DM
authors.lastname: Kallenberg
authors.forename: Carla
authors.initials: C
authors.lastname: Milagre
authors.forename: W
authors.initials: W
authors.lastname: Heung Chong
authors.forename: Jade
authors.initials: J
authors.lastname: Chow
authors.forename: Lucy
authors.initials: L
authors.lastname: Hill
authors.forename: Stacey
authors.initials: S
authors.lastname: Hoare
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Collinson
authors.forename: Mehnaz
authors.initials: M
authors.lastname: Hossain
authors.forename: W Nicol
authors.initials: WN
authors.lastname: Keith
authors.forename: Richard
authors.initials: R
authors.lastname: Marais
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
mesh_terms: D000705:Anaphase; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D016922:Cellular Senescence; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins