engleski

The role of androgen and androgen receptors in metastasis of head and neck tumors

Head and neck tumors originate anywhere on the mucosa of the upper respiratory and digestive tracts. They are sixth by incidence, with a frequency of 5% in men and 2% in women. They most often occur in people over 50 years of age, cause significant morbidity and mortality, and five-year survival is about 50%. The main causes are alcohol consumption and smoking, and human papillomavirus infection. Treatment is primarily surgical, with adjuvant chemo and radiotherapy. Over 40% of cases at the time of diagnosis already have a metastasis in the regional lymph node. Since these tumors are more common in men, we want to investigate the role of androgen and androgen receptors in the metastasis of head and neck tumors. As a cell model, we will use the cell lines FaDu (primary cancer) and Detroit 562 (metastasis), purchased from the ATCC (TCP-1012™, Manassas, VA, USA). We will use dihydrotestosterone (DHT) to activate androgen receptors and simvastatin for androgen depletion. We will assess the migratory ability of untreated and treated cells using wound healing assay and colony forming assay. In these cells and tissue samples of primary tumors, metastatic lymph nodes and healthy mucosa, we will determine the expression of genes for nuclear (AR) and membrane (CACNA1C, OXER1 and SLC39A9) androgen receptors using the qPCR method. Present results have shown that treatment with DHT increases, while simvastatin decreases migration of Detroit 562 cells, while in FaDu cells only inhibitory effect of simvastatin is observed. In addition, compared to a healthy mucosa, gene expression of AR is decreased, OXER1 and SLC39A9 increased, while CACNA1C is the same in metastases compared to primary tumors. These preliminary results indicate a potential role of androgen membrane receptors in metastasis of head and neck tumors, as well as therapeutic potential of statins for this type of tumors.

androgen ; androgen receptors ; HNSCC

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