Oral squamous cell carcinoma (OSCC) is one of the most common and deadliest malignancies in the head and neck region with the survival rate ranging between 25%-55%. Epithelial-mesenchymal transition (EMT) plays a major role in cancer progression and tissue invasion and is considered to be the key process associated with recurrence, lymph node metastasis and low survival rate in patients with OSCC. Studies have shown that Endothelin-1 (ET-1), a potent vasoconstrictor, promotes EMT in various human cancers. However, the role of Endothelin-1 in the progression of OSCC have not been explored.
Tumor tissues and adjacent clinically normal tissues were obtained from 75 patients with primary oral squamous cell carcinoma and 25 patients with recurrent OSCC. The expression of Endothelin-1 and EMT markers, SLUG, TWIST-1, E-cadherin and N-cadherin 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 were correlated with pathological grade, lymph node metastasis and AJCC staging of the tumor. Additionally, the expressions of ET-1 and TWIST-1 were evaluated in human OSCC cell lines using Western blot.
The mean immunoreactive scores of ET-1, SLUG, TWIST-1 and N-cadherin were higher in tumor tissues compared to adjacent normal tissue in patients with OSCC, whereas E-cadherin showed lower expression in OSCC samples. The tissue samples taken from recurrent cases of OSCC had higher expression of both Endothelin-1 and EMT markers than that of the primary OSCC. High-grade tumors and those with lymph node metastasis exhibited significantly increased immunohistochemical expression of ET-1, SLUG and TWIST-1 (p=0.01). Western blot analysis showed higher expression of ET-1 and TWIST-1proteins in OSCC cell lines. Knock down of ET-1 inhibited the migration and invasion of OSCC cells as demonstrated using transmigration assay.
Our study establishes the role of ET-1 in the progression of OSCC and hence, may represent a novel therapeutic target in the treatment of OSCC.
Jayanthi P, Vishnu Priya Veeraraghavan, Selvaraj Jayaraman.
Has not received any funding.
The author has declared no conflicts of interest.