Abstract
The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ETAR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cell malignancy and the expressions of ET-1 and ETAR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ETAR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.
Highlights
For many years in Japan, malignant tumors have been the most common cause of death, and due to aging of the population the number of cancer patients in the country has been increasing [1]
High levels of ET-1 expression were observed in the cytoplasm and cell membrane of the tumor cells, and high levels of ETAR expression were observed in the cell membrane of the tumor cells (Fig. 1)
In highly invasive squamous cell carcinoma, local progression and a high late metastasis rate is associated with a poor prognosis
Summary
For many years in Japan, malignant tumors have been the most common cause of death, and due to aging of the population the number of cancer patients in the country has been increasing [1]. This percentage is low, there are many patients with oral cancer for whom treatment is difficult, and poor outcomes despite treatment are often observed. In such a situation, drugs targeting molecules involved in cancer cell proliferation have been developed. ET-1 binds to ETAR with high affinity, and high expressions of ET-1 and ETAR in tumor tissue have been reported in patients with highly malignant prostatic cancer accompanied by bone metastasis [11, 12]
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