Understanding the Role of Polarity Regulators in Irradiated Salivary Glands Following Injury and During Regeneration

Abstract

Approximately 600,000 patients are diagnosed with head and neck cancer (HNC) worldwide with a 40-50% mortality rate each year. Malfunctioning salivary glands and consequential xerostomia is a common and chronic complication for patients treated with radiotherapy for HNC. While significant improvements have been achieved in the prevention and treatment of radiation-induced hyposalivation, many patients still suffer from xerostomia and other oral complications. This implies that the above-described strategies are not sufficient in restoring salivary function and secretion. Though there are efforts directed toward gene therapy, artificial salivary glands, and stem cell transplantation, these techniques are not fully standardized, nor clinically applicable yet. Considerable research efforts have focused on the role of radiation damage on the stem/progenitor cells (SPCs). Just as important, restoration of the salivary glands requires an understanding of the spatial and temporal interactions of its environment since it provides paracrine and mechanical signals to maintain the SPCs. Polarity, the intrinsic asymmetry of cellular components, plays a role in the reestablishment of the epithelization process that is necessary for directional salivary secretion. While polarity has been shown to be important in salivary development, homeostasis, and maintenance, the effects of radiation on polarity in the total parotid tissue remain largely unknown. The question of what polarity regulators are damaged, how they are damaged, and if they respond during tissue regeneration is still elusive. We propose that by understanding the role of polarity regulators following injury and during tissue regeneration, we would be able to elucidate some mechanistic insights that govern radiation-induced salivary dysfunction.