Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics

Abstract

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surgery, using Western blotting. Hsp27, Hsp60, and Hsp90 were increased in PC in comparison with PT and BG but no differences were found for Hsp70. Similarly, exosomal levels of Hsp27, Hsp60, and Hsp90 were higher in PC than in BG, and those in PC were higher before ablative surgery than after it. Hsp27, Hsp60, and Hsp90 show distinctive quantitative patterns in thyroid tissue and circulating exosomes in PC as compared with BG, suggesting some implication in the carcinogenesis of these chaperones and indicating their potential as biomarkers for clinical applications.

Molecular Chaperones and Thyroid Cancer

“…The level of Hsp27 was high but did not show a significant quantitative variation in cancerous tissues compared to the corresponding normal parenchyma, whereas Hsp60, Hsp70, and Hsp90 were increased in FTC compared to FA and/or to adjacent normal parenchyma [22]. In another study, the immunohistochemical levels of Hsp27, Hsp60, and Hsp90, but not Hsp70, were high in PTC as compared with benign goiters and normal peritumoral tissues [21]. Both works also reported the intracellular distribution of each Hsp, showing not only an increased level in cancerous compared to normal tissues, but also an altered localization, with accumulation in the cytoplasm and plasma cell membrane in cancerous specimens [21,22].…”

“…In another study, the immunohistochemical levels of Hsp27, Hsp60, and Hsp90, but not Hsp70, were high in PTC as compared with benign goiters and normal peritumoral tissues [21]. Both works also reported the intracellular distribution of each Hsp, showing not only an increased level in cancerous compared to normal tissues, but also an altered localization, with accumulation in the cytoplasm and plasma cell membrane in cancerous specimens [21,22]. These results agree with other works showing a change in the cellular distribution or even extracellular secretion of Hsps during carcinogenesis processes [61][62][63][64][65].…”

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application

“…Caruso et al found that the levels of Hsp27, Hsp60, and Hsp90 were increased in TPC tissue compared with normal peritumoral tissue and benign goiters. The levels of HSPs in the exosomes of patients with TPC before surgery were significantly higher than those in the exosomes from the same patients after surgery and from patients with benign goiters (122). TC is considered one of the most immunogenic cancers (123); thus, the rapid development of immunotherapy and exosomes as a delivery system brings new opportunities for the treatment of TC.…”

Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies

“…Moreover, patients with metastatic PTC have significantly higher levels of circulating exosomal miRNAs and hypoxic PTC cells can secrete exosomes that modulate the expression of TGF-β and collagen isoforms, enhancing the tumoral angiogenesis [ 192 ]. The exosomes secreted by CSCs also modulate the polarization of TAMs toward the M2 phenotype and suppress NK cell activity, promoting an immunosuppressive environment in CSC niches [ 193 , 194 , 195 , 196 ]. In turn, CAFs and TAMs also release exosomes that contribute to the regulation of the TME [ 187 , 197 , 198 ].…”