Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma

Lo Lin Tsai, Cheng Chia Yu, Yu Chao Chang, Chuan Hang Yu, Ming Yung Chou

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)621-628
Number of pages8
JournalJournal of Oral Pathology and Medicine
Volume40
Issue number8
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

Fingerprint

Cisplatin
Squamous Cell Carcinoma
Serial Passage
Neoplasms
Neoplastic Stem Cells
Mouth Neoplasms
Cell Movement
Up-Regulation
Immunohistochemistry
Staining and Labeling
Neoplasm Metastasis
Gene Expression
Recurrence

Keywords

  • Cancer stem cells
  • Chemo-resistance
  • Nanog
  • Oct4
  • Oral squamous cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oral Surgery
  • Periodontics

Cite this

Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma. / Tsai, Lo Lin; Yu, Cheng Chia; Chang, Yu Chao; Yu, Chuan Hang; Chou, Ming Yung.

In: Journal of Oral Pathology and Medicine, Vol. 40, No. 8, 09.2011, p. 621-628.

Research output: Contribution to journalArticle

Tsai, Lo Lin ; Yu, Cheng Chia ; Chang, Yu Chao ; Yu, Chuan Hang ; Chou, Ming Yung. / Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma. In: Journal of Oral Pathology and Medicine. 2011 ; Vol. 40, No. 8. pp. 621-628.
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abstract = "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.",
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AB - 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.

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