Cell division patterns and chromosomal segregation defects in oral cancer stem cells.
Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc.
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.|Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
Hatem O
HO
Kaseb
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
Dale W
DW
Lewis
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA.|University of Pittsburgh Cancer Institute, Pittsburgh, PA.
William S
WS
Saunders
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.|University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Susanne M
0000-0001-5438-6808
SM
Gollin
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D002455:Cell Division / Q000235:genetics* / Q000528:radiation effects; D020090:Chromosome Segregation / Q000235:genetics* / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D007259:Infrared Rays; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors