Abstract:
Very little is known about the molecular composition and function of thyroid colloid beyond its role as a thyroglobulin, iodine, and thyroid hormone storage depot. Colloid morphologic heterogeneity is observed in all major thyroid disorders with reduced colloid volume being a hallmark of thyroid cancer. Elucidating colloid protein content and its interactions with epithelial cells in thyroid follicles may provide new insights into tumor progression along with potentially actionable information on new therapeutic modalities to test in thyroid cancer patients. Multiplatform proteomic analyses of laser capture microdissected (LCM) follicular cells and colloid indicate that intracellular colloid is a heterogeneous proteinaceous fluid with the potential of regulating more than thyroid hormone synthesis. Presence of extracellular vesicles and protein expression of autophagy markers in tumor-associated thyroid cells suggests that cellular components are being degraded/recycled for energy while depleting essential proteins from the colloid, thus creating constant cell stress contributing to tumor proliferation. Establishing signatures of post-translational modifications within the colloid and epithelial cells could potentially be useful in effectively categorizing patients for prognostic and therapeutic purposes. Furthermore, the colloid characteristics may aid in early identification of patients showing key modifications indicative of tumor progression.
