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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification of very small cancer stem cells expressing hallmarks of pluripotency in B16F10 melanoma cells and their reoccurrence in B16F10-derived clones

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Author(s):
Dias Camara, Diana Aparecida [1, 2] ; de Sa Junior, Paulo Luiz [3] ; de Azevedo, Ricardo Alexandre [4] ; Figueiredo, Carlos Rogerio [5, 4] ; Araldi, Rodrigo Pinheiro [6] ; Levy, Debora [7] ; de Souza, Dener Madeiro [1] ; Kerkis, Irina [1]
Total Authors: 8
Affiliation:
[1] Butantan Inst, Lab Genet, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Programa Posgrad Biol Estrutural & Func, Sao Paulo, SP - Brazil
[3] Univ Mogi das Cruzes UMC, Villa Lobos Campus, Sao Paulo, SP - Brazil
[4] Univ Fed Sao Paulo, Microbiol Immunol & Parasitol Dept, Expt Oncol Unit UNONEX, Sao Paulo, SP - Brazil
[5] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside - England
[6] Univ Fed Sao Paulo, Lab Genet Basis Thyroid Canc, Sao Paulo - Brazil
[7] Univ Sao Paulo, Lab Genet & Mol Hematol LIM31, Sch Med, Sao Paulo, SP - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Experimental Cell Research; v. 391, n. 2 JUN 15 2020.
Web of Science Citations: 0
Abstract

Melanoma is characterized by high heterogeneity and plasticity, most likely due to the presence of mutated melanocyte stem cells or immature progenitor cells in the skin that serves as precursors to melanoma. In the present study, for the first time, we identified rare cells in the murine melanoma B16F10, and human A2058 and SK-MEL-28 cell lines that express pluripotency markers, including Oct4, Nanog, Sox2 and a marker of melanoma cancer cells (ALDH1/2). These cells are very small with round morphology and they grow onto melanoma cells, thereby demonstrating feeder layer dependence similar to that of other pluripotent cells. These cells underwent self-renewal, symmetric and asymmetric division. We called these cells murine very small cancer stem cells (VSCSC). VSCSC were also found in B16F10-derived clones after 3-5 consecutive passages, where they occur as single cells or as small colonies, nevertheless, always using melanoma cells as feeders. These cells formed melanospheres enriched with Oct4-and ALDH1/2-positive cells. We also evaluated the possible effect of VSCSC that presented in the parental cell line (B16F10) and in clones based on their functional characteristics. We found that VCSCS present in the B16F10 cell line reappearing in their clones were required for continuous tumor growth and were responsible for melanoma cell heterogeneity and plasticity rather than directly affecting functional characteristics of melanoma cells. Our data, together with those of previous reports suggested the existence of melanoma-competent melanocyte stem cells, which corroborate the hypothesis of the existence of tumor-initiating cells and cancer stem cell hierarchies, at least in melanoma. (AU)

FAPESP's process: 10/51051-6 - Adult stem cells versus induced pluripotent stem cells
Grantee:Irina Kerkis
Support Opportunities: Research Projects - Thematic Grants