Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma
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Abstract
Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4, and c-MYC in all samples, while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n = 6) and reverse-transcription quantitative polymerase chain reaction (n = 5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.
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Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
KLF4 is regulated by RAS/RAF/MEK/ERK signaling through E2F1 and promotes melanoma cell growth
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- Authors
- Yoganandarajah, V., Patel, J., van Schaijik, B., Bockett, N., Brasch, H. D., Paterson, E., Sim, D., Davis, P. F., Roth, I. M., Itinteang, T., & Tan, S. T.
- Affiliations
- Gillies McIndoe Research Institute (NZ)
- Gillies McIndoe Research Institute, Newtown, Wellington 6021, New Zealand
- University of Otago (NZ)
- The University of Melbourne (AU)
- Corresponding author
- Tan, Swee T.
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2020-01-30
- Volume
- 9
- Issue
- 2
- Pages
- 324
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC7072148
- OpenAlex
- W2980655955
- Cited by
- 26
- References
- 2
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 6
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cancer stem cells, Oct4, SOX2, KLF4, c-Myc, Nanog, tumor nests, peritumoral stroma, tumor spheres, regional lymph node metastasis, therapeutic target
- MeSH terms
- Kruppel-Like Factor 4, Aged, Aged, 80 and over, Female, Head and Neck Neoplasms, Humans, Male, Melanoma, Middle Aged, Neoplasm Proteins, RNA, Messenger, Transcription Factors, Transcription, Genetic, Neoplastic Stem Cells, Gene Expression Regulation, Neoplastic, Spheroids, Cellular, Cell Line, Tumor, Induced Pluripotent Stem Cells
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