Identification of very small cancer stem cells expressing hallmarks of pluripotency in B16F10 melanoma cells and their reoccurrence in B16F10-derived clones.
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Melanoma, Experimental
/ genetics
Mice
Mice, Inbred C57BL
Neoplastic Stem Cells
/ metabolism
Octamer Transcription Factor-3
/ genetics
Recurrence
SOXB1 Transcription Factors
/ genetics
Tumor Cells, Cultured
Cancer stem cells
Melanoma
Pluripotency factors
Symmetric and asymmetric division
Tumor initiating cells
Journal
Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
25
11
2019
revised:
28
02
2020
accepted:
01
03
2020
pubmed:
13
4
2020
medline:
1
1
2021
entrez:
13
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32278688
pii: S0014-4827(20)30143-9
doi: 10.1016/j.yexcr.2020.111938
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Octamer Transcription Factor-3
0
Pou5f1 protein, mouse
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111938Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing interests.