Abstract
Gp78/autocrine motility factor receptor (Gp78/AMFR) is a cancer-associated endoplasmic reticulum-localized E3 ubiquitin ligase and also the cell surface receptor for autocrine motility factor (AMF). The study objective was to determine the association between Gp78/AMFR and AMF endocytosis in thyroid cancer cells. Gp78/AMFR expression and AMF internalization were measured in differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC) cell lines and in freshly resected human papillary thyroid cancers (PTC) relative to benign thyroid tissue. Spheroid-like aggregates generated from explants of cancer, goiter, and collateral thyroid tissue were assessed for expression of cancer stem cell markers, surface Gp78/AMFR and AMF endocytosis. DTC cell lines showed elevated total and surface Gp78/AMFR and AMF internalization relative to ATC lines. Gp78/AMFR, Oct-4 and Sox-2 protein expression, Gp78/AMFR surface expression and AMF internalization were elevated in PTC-derived aggregates relative to fibroblasts. Elevated levels of Gp78/AMFR expression and AMF internalization in PTC were associated with expression of cancer stem cell markers. Gp78/AMFR expression and AMF uptake are more closely associated with DTC compared to benign thyroid lesions or ATC and with PTC-derived cancer stem-like cells.
Highlights
Thyroid nodules are extremely common in the general population, being palpable in 5% of people and diagnosed by high resolution ultrasound in greater than half of people
Gp78/AMFR expression and autocrine motility factor (AMF) internalization were measured in differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC) cell lines and in freshly resected human papillary thyroid cancers (PTC) relative to benign thyroid tissue
Spheroid-like aggregates generated from explants of cancer, goiter, and collateral thyroid tissue were assessed for expression of cancer stem cell markers, surface Gp78/AMFR and AMF endocytosis
Summary
Thyroid nodules are extremely common in the general population, being palpable in 5% of people and diagnosed by high resolution ultrasound in greater than half of people. Thyroid cancer tends to present as a thyroid nodule and, only a small minority of thyroid nodules are eventually diagnosed as being malignant [1]. The steady rise in thyroid cancer incidence, which has been observed for greater than 20 years, has largely been attributed to increased utilization of diagnostic imaging [1]. Thyroid cancers, evaluated in [2], included papillary carcinoma (PTC) (80-85%) and follicular carcinoma (FTC) (10-15%) that are generally grouped as differentiated thyroid cancer (DTC), as well as highly aggressive anaplastic thyroid cancer (ATC) (1-2%) believed to arise from pre-existing DTC. The vast majority of DTC patients who undergo thyroid cancer treatment have an excellent prognosis.
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