Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma
Version of Record online: 22 FEB 2011
© 2011 John Wiley & Sons A/S
Journal of Oral Pathology & Medicine
Volume 40, Issue 8, pages 621–628, September 2011
How to Cite
Tsai, L.-L., Yu, C.-C., Chang, Y.-C., Yu, C.-H. and Chou, M.-Y. (2011), Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma. Journal of Oral Pathology & Medicine, 40: 621–628. doi: 10.1111/j.1600-0714.2011.01015.x
- Issue online: 2 SEP 2011
- Version of Record online: 22 FEB 2011
- Accepted for publication January 11, 2011
- cancer stem cells;
- oral squamous cell carcinoma
J Oral Pathol Med (2011) 40: 621–628
Background: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide. Cancer stem cells (CSC) model theoretically contribute to tumor growth, metastasis, and chemo-radioresistance. Cisplatin is a widely used chemotherapeutic agent for OSCC treatment. The aim of this study was to compare stemness genes expression in chemo-sensitive and chemo-resistant specimens and further explore the potential markers that may lead to induce chemo-resistance in OSCC.
Methods: The study method is the treatment of OC2 cells with cisplatin select cisplatin-resistant OC2 cells. Self-renewal ability was evaluated by cultivating parental and cisplatin-resistant OC2 cells within sphere-forming assay after serial passages. Differential expression profile of stemness markers between parental and cisplatin-resistant OC2 cells was elucidated. The parental and cisplatin-resistant OC2 cells were assessed for migration/invasion/clonogenicity tumorigenic properties in vitro. Expression of stemness markers in chemo-sensitive and chemo-resistant patients with OSCC was performed by immunohistochemistry staining in vivo.
Results: Sphere-forming/self-renewal capability was increased in cisplatin-resistant OC2 cells. Cisplatin-resistant OC2 cells highly expressed the stemness markers (Nanog, Oct4, Bmi1, CD117, CD133, and ABCG2). Furthermore, cisplatin-resistant OC2 cells increased migration/invasion/clonogenicity ability. Notably, up-regulation of Oct4 and Nanog expression was significantly observed in cisplatin-resistant patients with OSCC (**P < 0.01).
Conclusions: These data indicate that cancer stem-like properties were expanded during the acquisition of cisplatin resistance in OSCC. Clinically, oral cancer stemness markers (Oct4 and Nanog) overexpression may promote the OSCC’s recurrence to resist cisplatin.