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鉴定头颈部转移性恶性黑色素瘤中的癌症干细胞亚群。

Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma.

机构信息

Gillies McIndoe Research Institute, Newtown, Wellington 6021, New Zealand.

Biostatistical Group/Dean's Department, University of Otago, Wellington 6242, New Zealand.

出版信息

Cells. 2020 Jan 30;9(2):324. doi: 10.3390/cells9020324.

DOI:10.3390/cells9020324
PMID:32019273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072148/
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 ( = 6) and reverse-transcription quantitative polymerase chain reaction ( = 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.

摘要

癌症干细胞 (CSCs) 已在许多癌症类型中被鉴定出来。本研究使用诱导多能干细胞 (iPSC) 标志物鉴定并表征了头颈部转移性恶性黑色素瘤 (HNmMM) 至区域淋巴结中的 CSCs。对 20 个 HNmMM 组织样本进行免疫组织化学 (IHC) 染色，结果显示所有样本均表达 iPSC 标志物 OCT4、SOX2、KLF4 和 c-MYC，而 NANOG 在两个样本中低表达。免疫荧光 (IF) 染色显示 HNmMM 组织中肿瘤巢 (TN) 内存在 OCT4+/SOX2+/KLF4+/c-MYC+ 的 CSC 亚群，另一个存在于肿瘤周围基质 (PTS) 内。IF 还显示了在一个表达 NANOG 的 HNmMM 组织样本中，TN 内的一些 OCT4+/SOX2+/KLF4+/c-MYC+细胞表达 NANOG。对 HNmMM 样本进行的原位杂交 (= 6) 和逆转录定量聚合酶链反应 (= 5) 证实了所有五个 iPSC 标志物的表达。对 20 个 HNmMM 组织样本中的 4 个衍生的原代细胞系进行 Western blot 分析显示 SOX2、KLF4 和 c-MYC 的表达，但 OCT4 和 NANOG 的表达则不然，其中 3 个细胞系在体外形成肿瘤球体。我们证明了 HNmMM 中存在两个潜在的 CSC 亚群，这可能是治疗这种侵袭性癌症的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/ddaaa97ea270/cells-09-00324-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/cb1b4d3d86a9/cells-09-00324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/6190e115498a/cells-09-00324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/c9e30f46c1d3/cells-09-00324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/7f6f0a3b672d/cells-09-00324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/ce9abd149cf9/cells-09-00324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/77445f472a3b/cells-09-00324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/c2c6ce86e733/cells-09-00324-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/ddaaa97ea270/cells-09-00324-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/cb1b4d3d86a9/cells-09-00324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/6190e115498a/cells-09-00324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/c9e30f46c1d3/cells-09-00324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/7f6f0a3b672d/cells-09-00324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/ce9abd149cf9/cells-09-00324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/77445f472a3b/cells-09-00324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/c2c6ce86e733/cells-09-00324-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c613/7072148/ddaaa97ea270/cells-09-00324-g008.jpg

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