Abstract
Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.
Highlights
Using conventional hematoxylin and eosin (HE) staining, resected normal parotid gland tissue specimens appeared as parenchymal tissue divided into lobules by the stromal fibrous connective tissue septa in which large excretory interlobular ducts were seen under lower magnification (Figure 1A,J)
We found a characteristically higher expression of ATP binding cassette subfamily D3 (ABCD3) in parotid tumor cells compared to their healthy counterpart, suggesting an enhanced lipid trafficking across peroxisomes
We demonstrated the presence of differential expression of peroxisomal proteins between healthy and tumor tissue of the human parotid salivary gland
Summary
Salivary gland cancers are rare neoplasms accounting for 3–6% of all head and neck cancers with an annual incidence of 16/1,000,000 population, a 5-year survival rate of 95%. If confined to gland and a 44% survival rate in the case of distant metastasis [1,2,3]. In this case, 80% of those tumors arise in the parotid gland, 10–15% arising in the submandibular gland, and the remainder arising in sublingual and minor salivary glands [4]. We focused our experiments on deciphering peroxisome characteristics in the above three prevalent parotid gland histopathological tumor types
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