Subin Surendran1, Gangotri Siddappa2, Amrutha Mohan3, Wesley Hicks1, Vijayvel Jayaprakash1, Christina Mimikos1, Mohammed Mahri1, Fatima Almarzouki1, Kayla Morrell4, Ravindra Ravi5, Sindhu Govindan2, C N Sushma6, Nisheena Raghavan7, Praveen Birur6, Jeyaram Ilayaraja8, Mihai Merzianu9, Mary Reid10, Amritha Suresh11, Moni Abraham Kuriakose12. 1. Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, USA. 2. Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India. 3. Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, USA; Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA. 4. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, USA. 5. Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India; Head and Neck Oncology, Mazumdar Shaw Medical Centre, Bangalore, India. 6. Department of Oral Medicine and Radiology, KLE Institute of Dental Sciences, Dental Hospital and Research Centre, Bangalore, India. 7. Department of Pathology, Mazumdar Shaw Medical Center, Bangalore, India. 8. Department of Clinical Research, Mazumdar Shaw Medical Center, Bangalore, India. 9. Pathology, Roswell Park Cancer Institute, Buffalo, USA. 10. Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA. 11. Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India; Head and Neck Oncology, Mazumdar Shaw Medical Centre, Bangalore, India; Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, USA. 12. Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, USA; Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India; Head and Neck Oncology, Mazumdar Shaw Medical Centre, Bangalore, India; Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, USA. Electronic address: moni.kuriakose@roswellpark.org.
Abstract
OBJECTIVE: The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. MATERIALS AND METHODS: Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p < 0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; p < 0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; p = 0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high (p < 0.05) and CD31high/SDF1high (p = 0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant disorders and may hence be used in identifying high-risk OPMD. Published by Elsevier Ltd.
OBJECTIVE: The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. MATERIALS AND METHODS:Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p < 0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; p < 0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; p = 0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high (p < 0.05) and CD31high/SDF1high (p = 0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant disorders and may hence be used in identifying high-risk OPMD. Published by Elsevier Ltd.
Authors: Qinghua Zeng; Shenglin Li; Douglas B Chepeha; Thomas J Giordano; Jong Li; Honglai Zhang; Peter J Polverini; Jacques Nor; Jan Kitajewski; Cun-Yu Wang Journal: Cancer Cell Date: 2005-07 Impact factor: 31.743
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Authors: Subin Surendran; Usama Aboelkheir; Andrew A Tu; William J Magner; S Lynn Sigurdson; Mihai Merzianu; Wesley L Hicks; Amritha Suresh; Keith L Kirkwood; Moni A Kuriakose Journal: Biomedicines Date: 2022-07-30