Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD...

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Main Authors: Simple Mohanta, Gangotri Siddappa, Sindhu Govindan Valiyaveedan, Ravindra Dodda Thimmasandra Ramanjanappa, Debashish Das, Ramanan Pandian, Samanta Sekhar Khora, Moni Abraham Kuriakose, Amritha Suresh
Format: Article
Language:English
Published: SAGE Publishing 2017-05-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317703656
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author Simple Mohanta
Gangotri Siddappa
Sindhu Govindan Valiyaveedan
Ravindra Dodda Thimmasandra Ramanjanappa
Debashish Das
Ramanan Pandian
Samanta Sekhar Khora
Moni Abraham Kuriakose
Amritha Suresh
author_facet Simple Mohanta
Gangotri Siddappa
Sindhu Govindan Valiyaveedan
Ravindra Dodda Thimmasandra Ramanjanappa
Debashish Das
Ramanan Pandian
Samanta Sekhar Khora
Moni Abraham Kuriakose
Amritha Suresh
author_sort Simple Mohanta
collection DOAJ
description Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44 high /CD147 high cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial–mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.
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spelling doaj-art-29893d0d7f86482391e4cd1af4e0f9602025-08-20T03:32:58ZengSAGE PublishingTumor Biology1423-03802017-05-013910.1177/1010428317703656Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinomaSimple Mohanta0Gangotri Siddappa1Sindhu Govindan Valiyaveedan2Ravindra Dodda Thimmasandra Ramanjanappa3Debashish Das4Ramanan Pandian5Samanta Sekhar Khora6Moni Abraham Kuriakose7Amritha Suresh8Department of Head and Neck Oncology, Mazumdar Shaw Medical Center, Narayana Hrudayalaya, Bangalore, IndiaIntegrated Head and Neck Oncology Program, DSRG-5, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health City, Bangalore, IndiaIntegrated Head and Neck Oncology Program, DSRG-5, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health City, Bangalore, IndiaDepartment of Head and Neck Oncology, Mazumdar Shaw Medical Center, Narayana Hrudayalaya, Bangalore, IndiaStem Cell Research Lab, GROW Lab, Narayana Nethralaya Foundation, Bangalore, IndiaGROW Lab, Narayana Nethralaya Foundation, Bangalore, IndiaSchool of Bio Sciences & Technology, Vellore Institute of Technology (VIT) University, Vellore, IndiaMazumdar Shaw Medical Centre–Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, NY, USAMazumdar Shaw Medical Centre–Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, NY, USADifferentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44 high /CD147 high cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial–mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.https://doi.org/10.1177/1010428317703656
spellingShingle Simple Mohanta
Gangotri Siddappa
Sindhu Govindan Valiyaveedan
Ravindra Dodda Thimmasandra Ramanjanappa
Debashish Das
Ramanan Pandian
Samanta Sekhar Khora
Moni Abraham Kuriakose
Amritha Suresh
Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
Tumor Biology
title Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
title_full Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
title_fullStr Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
title_full_unstemmed Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
title_short Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
title_sort cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma
url https://doi.org/10.1177/1010428317703656
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