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

• Published in: Tumor biology 2017-06, Vol.39 (6), p.1010428317703656-1010428317703656
• Main Authors: Mohanta, Simple, Siddappa, Gangotri, Valiyaveedan, Sindhu Govindan, Dodda Thimmasandra Ramanjanappa, Ravindra, Das, Debashish, Pandian, Ramanan, Khora, Samanta Sekhar, Kuriakose, Moni Abraham, Suresh, Amritha
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Authorship; Basigin - genetics; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; CD147 antigen; CD44 antigen; Cell Differentiation - genetics; Cell Movement - genetics; Cell Self Renewal - genetics; Cell self-renewal; Female; Flow cytometry; Gene expression; Head & neck cancer; Histology; Humans; Hyaluronan Receptors - genetics; Male; Medical prognosis; Mesenchyme; Metastasis; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Neoplasm Invasiveness - genetics; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Oral cancer; Oral squamous cell carcinoma; Patients; Pattern formation; Prognosis; Squamous cell carcinoma; Stem cells; Tumor cell lines; Tumors
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317703656

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 CD44high/CD147high 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 CD44high/CD147high 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.