Heat shock proteins in embryonic and adult submandibular salivary glands in healthy and tumorigenic tissues

FASEB JOURNAL(2020)

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摘要
Introduction Heat Shock Proteins (HSPs) role in development and function of human salivary glands have not yet been measured or mapped in detail, in particular, HSP60 role is unknown. They can be potential biomarkers for glandular diseases and malignancies. We present our initial findings on HSP10, HSP27, HSP60, HSP70 and HSP90 distribution in human submandibular salivary glands (SMG) at various stages of development and tumorigenesis. Methods Adult human SMG (normal and tumoral) and embryonic head tissue samples were processed by standard methods for routine histological analysis and immunohistochemical staining using antibodies against the five HSP’s. All procedures were in accordance with the Helsinki Declaration. In addition, proteins and RNAs were extracted from normal SMG of FVB-NJ adult mice. Protein and gene expression of HSPs were assessed by western blot and RT-PCR respectively. Results HSP27, HSP60 and HSP90 were present in the acini and ducts of embryonic salivary glands but had a different distribution pattern in adult glands: HSP27, HSP60 and HSP10 occurred only in the ducts whereas HSP90 and HSP70 were totally absent in the adult gland. The results were supported by our western blot and RT-PCR as HSP10, HSP27 and HSP60 protein and mRNA were expressed in control adult mice SMG. HSP70 and HSP90 protein and mRNA were not expressed in adult mice SMG, thus matching our immunohistochemical results. In contrast, all 5 HSP’s levels were high in Pleomorphic Adenoma, Warthin’s tumor and Adenoid Cystic Adenoma. Conclusions The HSP27, HSP60 and HSP90 participate actively in the developmental process. HSP’s are also involved in neoplasm formation and progression. These results support the diagnostic and prognostic potentials of HSP’s. Significance Salivary glands tumors incidence is increasing, which makes it necessary to develop diagnostic tools and biometrics to understand the molecular mechanisms involved. Since molecular chaperones show quantitative variations and contribute to the carcinogenic mechanism in a variety of cancers, we aimed to investigate if a similar situation occurs in salivary glands and characterize the functions of the chaperoning system in physiology and pathology in these glands. Our findings exhibited quantitative patterns of the HSP’s, which can distinguish between normal and tumor tissues of the SMG and have potential in diagnosis and patient monitoring.
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submandibular salivary glands,heat shock proteins
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