Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

Abstract

To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.

Multi-element analysis of metals in human pathological and unchanged thyroid glands – pilot study

“…There are studies that prove that Mg and Ca supplementation has a positive effect on sugar metabolism in patients with type 2 diabetes, as it influences β-cell functioning and acts as a cofactor of many enzymes involved in the glucose level lowering [ 44 ]. Intensive glycation, leading to the formation of advanced glycation end products (AGEs), including pentosidine, is a very unfavourable process, which can also initiate and accelerate cancer formation, including the thyroid gland cancer [ 45 , 46 ]. If the anti-glycation effects of calcium and magnesium are confirmed, it will be important information for endocrinologists dealing with diabetes and thyroid diseases.…”

The role of glycans in the mechanobiology of cancer

“…Receptor for advanced glycation end products (RAGE) are multiligand-specific receptors that bind AGEs and are upregulated in cancer ( 196 ). Numerous RAGE inhibitors have been identified to target the AGE/RAGE axis in cancer ( 197 , 198 , 199 , 200 ).…”

Could Oxidative Stress Play a Role in the Development and Clinical Management of Differentiated Thyroid Cancer?

“…It is also important to consider the potential confounding effects of comorbidities and other factors that may affect OS biomarkers in TC patients. Further research is needed to identify the most reliable and specific OS biomarkers for TC, as well as to determine the optimal timing and frequency of OS biomarker measurements during treatment and follow-up [ 124 ].…”