ABSTRACT
Cancer stem cells (CSCs) are cells within tumors that maintain the ability to self-renew, drive tumor growth, and contribute to therapeutic resistance and cancer recurrence. In this study, we investigate the role of Zinc finger and SCAN domain containing 4 (ZSCAN4) in human head and neck squamous cell carcinoma (HNSCC). The murine Zscan4 is involved in telomere maintenance and genomic stability of mouse embryonic stem cells. Our data indicate that the human ZSCAN4 is enriched for, marks and is co-expressed with CSC markers in HNSCC. We show that transient ZSCAN4 induction for just 2 days increases CSC frequency both in vitro and in vivo and leads to upregulation of pluripotency and CSC factors. Importantly, we define for the first time the role of ZSCAN4 in altering the epigenetic profile and regulating the chromatin state. Our data show that ZSCAN4 leads to a functional histone 3 hyperacetylation at the promoters of OCT3/4 and NANOG, leading to an upregulation of CSC factors. Consistently, ZSCAN4 depletion leads to downregulation of CSC markers, decreased ability to form tumorspheres and severely affects tumor growth. Our study suggests that ZSCAN4 plays an important role in the maintenance of the CSC phenotype, indicating it is a potential therapeutic target in HNSCC.
Subject(s)
Carcinoma, Squamous Cell/genetics , Chromatin Assembly and Disassembly/genetics , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Neoplastic Stem Cells/metabolism , Transcription Factors/genetics , Acetylation , Animals , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/therapy , Cell Line, Tumor , DNA-Binding Proteins/metabolism , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/therapy , Histones/metabolism , Humans , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Nanog Homeobox Protein/genetics , Nanog Homeobox Protein/metabolism , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , Phenotype , RNA Interference , Transcription Factors/metabolism , Xenograft Model Antitumor Assays/methodsABSTRACT
Chronic hematomas are defined as hematomas with slow, progressive growth over many weeks. They are an extremely rare cause of acute neck swelling in the pediatric population. They consist of an organized central mass of blood with granulation tissue and fibrotic changes peripherally. The presence of a capsule prevents resorption but allows for intracapsular bleeding with subsequent expansion. We describe a case of a 6-year-old girl who presented to the emergency department with a spontaneously occurring left neck mass in the supraclavicular region. A possible neoplasm was suggested on imaging. The patient was referred to a head and neck surgeon, she underwent a thorough workup, and the mass was ultimately surgically excised. Histologically, the mass was confirmed to be a chronic hematoma. The patient recovered uneventfully, and there has been no recurrence.
