Functional analysis of ESM1 by siRNA knockdown in primary and metastatic head and neck cancer cells

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Head and neck cancers are common types of cancer worldwide with approximately 650 000 new cases diagnosed each year, an estimated 350 000 of which result in death. Also, head and neck cancers constitute 4% of all cancer incidence.1 A variety of genetic and environmental factors contribute to the development of head and neck cancer. Among the important risk factors for head and neck cancer are exposure to carcinogens, tobacco and alcohol use, human papilloma virus (HPV) infection and genetic predispositions.2 The leading method of treatment for head and neck cancer is still surgery. Additionally, radiotherapy and chemotherapy are used. Surgical treatment causes significant damage to the patient's face, mouth, and laryngopharynx, which leads to severe swallowing disorders and directly affects speech, all of which greatly reduces quality of life in patients with cancer.6 Therefore, the development of supportive alternative methods of diagnosis and treatment is necessary. It is thought that our ever‐increasing knowledge of the human genome will allow the use of molecular methods in diagnosis and treatment.
ESM1 (endothelial cell‐specific molecule‐1), also known as Endocan, was originally cloned from a human endothelial cell cDNA library in 1996.9 ESM1 is a 50 kDa soluble proteoglycan; the mature polypeptide consists of 165 amino acids and includes a single dermatan sulfate chain covalently linked to the serine residue at position 137.9 ESM1 has been identified as a dermatan sulfate proteoglycan that can circulate freely in the bloodstream.11 Overexpression of ESM1 has an important role in tumor growth, development, and angiogenesis.12 It is now known that ESM1 is expressed in several types of cancer and that it affects cell survival and migration. Recent studies showed that ESM1 expression significantly affects the proliferation and migration of cells in colorectal, gastric, nasopharyngeal, and hepatocellular carcinomas.15 To the best of our knowledge, to date, there has not been any study of ESM1 in cancers of the head and neck. The head and neck region of the body is rich in lymphatic vessels, and nodal metastases here are prevalent.
Investigation of the effect of ESM1 in primary tumors and metastases may result in its use as a prognostic marker for patients with head and neck cancer. To this end, we transfected cells with siRNA to silence ESM1 expression. Subsequently, we investigated the effect of this gene through various molecular analyses. We characterized gene expression levels as well as cellular proliferation and migration to better understand the effects of this gene in the cell lines. The results of these analyses are an important first step in illuminating the basic effects of ESM1 in head and neck cancer.

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