Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/2/324 |
| _version_ | 1827833960214822912 |
|---|---|
| author | Vithushiya Yoganandarajah Josie Patel Bede van Schaijik Nicholas Bockett Helen D. Brasch Erin Paterson Dalice Sim Paul F. Davis Imogen M. Roth Tinte Itinteang Swee T. Tan |
| author_facet | Vithushiya Yoganandarajah Josie Patel Bede van Schaijik Nicholas Bockett Helen D. Brasch Erin Paterson Dalice Sim Paul F. Davis Imogen M. Roth Tinte Itinteang Swee T. Tan |
| author_sort | Vithushiya Yoganandarajah |
| collection | DOAJ |
| description | 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 (<i>n</i> = 6) and reverse-transcription quantitative polymerase chain reaction (<i>n</i> = 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. |
| first_indexed | 2024-03-12T05:40:57Z |
| format | Article |
| id | doaj.art-e23ba3228c4d4e57a84859552c72d91a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:40:57Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e23ba3228c4d4e57a84859552c72d91a2023-09-03T06:03:10ZengMDPI AGCells2073-44092020-01-019232410.3390/cells9020324cells9020324Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant MelanomaVithushiya Yoganandarajah0Josie Patel1Bede van Schaijik2Nicholas Bockett3Helen D. Brasch4Erin Paterson5Dalice Sim6Paul F. Davis7Imogen M. Roth8Tinte Itinteang9Swee T. Tan10Gillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandBiostatistical Group/Dean’s Department, University of Otago, Wellington 6242, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandGillies McIndoe Research Institute, Newtown, Wellington 6021, New ZealandCancer 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 (<i>n</i> = 6) and reverse-transcription quantitative polymerase chain reaction (<i>n</i> = 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.https://www.mdpi.com/2073-4409/9/2/324malignant melanomahead and neck cancercancer stem cellinduced pluripotent stem cellmelanoma metastasis |
| spellingShingle | Vithushiya Yoganandarajah Josie Patel Bede van Schaijik Nicholas Bockett Helen D. Brasch Erin Paterson Dalice Sim Paul F. Davis Imogen M. Roth Tinte Itinteang Swee T. Tan Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma Cells malignant melanoma head and neck cancer cancer stem cell induced pluripotent stem cell melanoma metastasis |
| title | Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma |
| title_full | Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma |
| title_fullStr | Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma |
| title_full_unstemmed | Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma |
| title_short | Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma |
| title_sort | identification of cancer stem cell subpopulations in head and neck metastatic malignant melanoma |
| topic | malignant melanoma head and neck cancer cancer stem cell induced pluripotent stem cell melanoma metastasis |
| url | https://www.mdpi.com/2073-4409/9/2/324 |
| work_keys_str_mv | AT vithushiyayoganandarajah identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT josiepatel identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT bedevanschaijik identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT nicholasbockett identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT helendbrasch identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT erinpaterson identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT dalicesim identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT paulfdavis identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT imogenmroth identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT tinteitinteang identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma AT sweettan identificationofcancerstemcellsubpopulationsinheadandneckmetastaticmalignantmelanoma |