Peroxiredoxin I, platelet-derived growth factor A, and platelet-derived growth factor receptor α are overexpressed in carcinoma ex pleomorphic adenoma: association with malignant transformation

Carcinoma ex pleomorphic adenoma is a rare salivary gland malignancy. It constitutes an important model for the study of carcinogenesis, as it can display the tumor in different stages of progression, from benign pleomorphic adenoma to frankly invasive carcinoma. Growth signaling pathways undergo continuous activation in human tumors, commonly as a consequence of the overexpression of ligands and receptors such as platelet-derived growth factor and platelet-derived growth factor receptor. Hydrogen peroxide is produced after platelet-derived growth factor receptor activation, and it is essential for the sequential phosphorylation cascade that drives cell proliferation and migration. By their ability to degrade hydrogen peroxide, peroxiredoxins are involved in growth factor signaling regulation and in the oxidative stress response. To verify the potential association of peroxiredoxin 1, platelet-derived growth factor-A, and platelet-derived growth factor receptor-a with carcinoma ex pleomorphic adenoma progression, we investigated the expression of these molecules in carcinoma ex pleomorphic adenoma showing different degrees of invasion. The peroxiredoxin 1, platelet-derived growth factor-A, and platelet-derived growth factor receptor-a proteins were present in remnant pleomorphic adenoma to only a small extent, but, collectively, they were highly expressed as soon as the malignant phenotype was achieved and remained at elevated concentrations during progression to the advanced stages of carcinoma ex pleomorphic adenoma. In addition, their locations overlapped significantly, strengthening their connection to this growth-signaling pathway. Our results indicate that carcinoma ex pleomorphic adenoma cells acquire at least 2 significant advantages relative to their normal counterparts: resistance to oxidative stress-induced apoptosis, conferred by high peroxiredoxin I concentrations, and sustained growth, reflecting platelet-derived growth factor-A and platelet-derived growth factor receptor-a overexpression. (c) 2009 Elsevier Inc. All rights reserved.