234P - Epithelial-mesenchymal transition and cancer stem cells: Missing link in oral squamous cell carcinoma

Background

Cancer stem cells (CSCs) are a heterogeneous population of cancer cells with characteristics similar to normal stem cells, including the ability for self-renewal and differentiation. CSCs can differentiate into tumor-supporting cells potentially enabling metastasis, relapse, and chemoresistance. Complex networks involving several transcription factors, such as Nanog, Oct4, SOX2, and various miRNAs, have been identified to regulate CSC properties. The EMT is a process in which epithelial cells change their morphology, lose their polarity and acquire the migratory properties of mesenchymal cells. Many reports have shown that cells undergoing EMT can acquire stem cell-like characteristics and express markers of the EMT. However, the correlation between stemness and EMT is still unclear in oral squamous cell carcinomas.

Methods

Tumor tissues and adjacent clinically normal tissues were obtained from 50 patients with primary oral squamous cell carcinoma (OSCC) and 40 patients with recurrent OSCC. The expression of CSC markers Nanog, SOX2, and OCT4 and EMT markers SLUG and TWIST-1 were analyzed using immunohistochemistry. The mean immunoreactive score (staining intensity x proportion of positive cells) was calculated and compared in both tumor tissue and adjacent tissue. The immunohistochemical expression of these markers was correlated with pathological grade, lymph node metastasis, and AJCC staging of the tumor. Additionally, the expressions of SOX-2 and SLUG were evaluated in human OSCC cell lines using Western blot.

Results

The mean immunoreactive score of Nanog, SOX2, OCT4, SLUG and TWIST-1was higher in tumor tissues compared to adjacent tissue. Likewise, higher expression of both CSC and EMT markers was noted in recurrent OSCC than primary OSCC. High-grade tumors and those showing lymph node metastasis exhibited significantly increased expression of SOX-2, OCT4, and SLUG (p<0.01). Western blot analysis showed higher expression of SOX-2 and SLUG proteins in OSCC cells. Knockdown of SOX-2 and SLUG inhibited the migration and invasion of OSCC cells as demonstrated using transmigration assay.

Conclusions

The present study provides novel insights into the potential association between CSCs and EMT in OSCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.