Abstract
The salivary glands are key components of the mouth and play a central role in its physiology. Their importance may be appreciated considering their number, occurrence in pairs, and distribution in the mouth: two parotids, two submandibular, two sublingual, and many other small ones scattered throughout the mouth. They produce saliva, without which ingestion of non-liquid nutrients and speech would be practically impossible. Nevertheless, the physiology and pathology of salivary glands are poorly understood. For instance, tumors of salivary glands occur, and their incidence is on the rise, but their etiology and pathogenesis are virtually unknown, although some risk factors have been identified. Likewise, the role of the chaperoning system in the development, normal functioning, and pathology, including carcinogenesis, remains to be determined. This scarcity of basic knowledge impedes progress in diagnosis, disease monitoring, and therapeutics of salivary gland tumors. We are currently involved in examining the chaperoning system of human salivary glands and we performed a search of the literature to determine what has been reported relating to oncology. We found data pertaining to six components of the chaperone system, namely HSP27, HSP60, HSP70, HSP84, HSP86, and GRP78, and to another HSP, the heme-oxygenase H-O1, also named HSP32, which does not belong in the chaperoning system but seemed to have potential as a biomarker for diagnostic purposes as much as the HSP/chaperones mentioned above. The reported quantitative variations of the six chaperones were distinctive enough to distinguish malignant from benign tumors, suggesting that these molecules hold potential as biomarkers useful in differential diagnosis. Also, the quantitative variations described accompanying tumor development, as observed in cancers of other organs, encourages research to elucidate whether chaperones play a role in the initiation and/or progression of salivary gland tumors.
Similar content being viewed by others
References
Acharya S, Mandal P (2016) Salivary IgA and dental caries in HIV patients: a pilot study. J Indian Soc Pedod Prev Dent 34(4):341
Aiko K, Tsujisawa T, Koseki T et al (2002) Involvement of cytochrome c and caspases in apoptotic cell death of human submandibular gland ductal cells induced by concanamycin A. Cell Signal 14(8):717–722
Araya J, Martinez R, Niklander S et al (2015) Incidence and prevalence of salivary gland tumours in Valparaiso, Chile. Med Oral Patol Oral Cir Bucal 20(5):e532–e539
Bachar G, Raiter A, Gilat H et al (2014) Apoptosis and cell surface GRP78 expression in benign and malignant parotid gland tumors. Head Neck Oncol 6(2):15
Bello IO, Salo T, Dayan D et al (2012) Epithelial salivary gland tumors in two distant geographical locations, Finland (Helsinki and Oulu) and Israel (Tel Aviv): a 10-year retrospective comparative study of 2,218 cases. Head Neck Pathol 6(2):224–231
Cappello F, Mazzola M, Jurjus A et al (2019) Hsp60 as a novel target in IBD management: a prospect. Front Pharmacol 10:26
Carpenter GH (2013) The secretion, components, and properties of saliva. Annu Rev Food Sci Technol 4(1):267–276
Chen W, Ren X, Wu J et al (2018) HSP27 associates with epithelial-mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma. J Cel Mol Med 22(4):2283–2298
Daneshmand S, Quek ML, Lin E et al (2007) Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. Hum Pathol 38(10):1547–1552
de Ridder G, Ray R, Misra UK et al (2011) Modulation of the unfolded protein response by GRP78 in prostate cancer. Methods Enzymol 489:245–257
de Siqueira EC, Souza FTA, Diniz MG et al (2015) Hsp27 (HSPB1) differential expression in normal salivary glands and pleomorphic adenomas and association with an increased Bcl2/Bax ratio. Tumor Biol 36(1):213–217
Del Signore AG, Megwalu UC (2017) The rising incidence of major salivary gland cancer in the United States. Ear Nose Throat J 96(3):E13–E16
Dong C, Hemminki K (2001) Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958–1996: a search for common mechanisms. Br J Cancer 85(7):997–1005
Ellis H (2012) Anatomy of the salivary glands. Surgery 30(11):569–572
Fu Y, Li J, Lee AS (2007) GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Res 67(8):3734–3740
Galdirs TM, Kappler M, Reich W et al (2019) Current aspects of salivary gland tumors—a systematic review of the literature. GMS Interdiscip Plast Reconstr Surg DGPW 8:Doc12
Girdler R, Odell E, Putnam G (2016) Epidemiology and management of major salivary gland cancers. Public Health England, London
Ho K, Lin H, Ann DK et al (2011) An overview of the rare parotid gland cancer. Head Neck Oncol 3(1):40
Kessler AT, Bhatt AA (2018) Review of the major and minor salivary glands, part 1: anatomy, infectious, and inflammatory processes. J Clin Imaging Sci 8:47
Lo S, Di Palma S, Yusuf H et al (2005) Constitutive (HO-2) and inducible (HO-1) haem oxygenase in pleomorphic adenomas of the human parotid: an immunocytochemical study. J Laryngol Otol 119(3):179–183
Macario AJL, Conway de Macario E (2019) Chaperone proteins and chaperonopathies. Stress Physiol Biochem Pathol 3:135–152
Macario AJL, Conway de Macario E, Cappello F (2013) The chaperonopathies: diseases with defective molecular chaperones. Springer, Dordrecht
Mancuso TF, Brennan MJ (1970) Epidemiological considerations of cancer of the gallbladder, bile ducts and salivary glands in the rubber industry. J Occup Med 12(9):333–341
Ni M, Zhang Y, Lee AS (2011) Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem J 434(2):181–188
Parkin DM, Ferlay J, Curado MP et al (2010) Fifty years of cancer incidence: CI5 I-IX. Int J Cancer 127(12):2918–2927
Pfaffenbach KT, Lee AS (2011) The critical role of GRP78 in physiologic and pathologic stress. Curr Opin Cell Biol 23(2):150–156
Radoï L, Barul C, Menvielle G et al (2018) Risk factors for salivary gland cancers in France: results from a case-control study, the ICARE study. Oral Oncol 80:56–63
Rappa F, Sciume C, Lo Bello M, et al (2014) Comparative analysis of Hsp10 and Hsp90 expression in healthy mucosa and adenocarcinoma of the large bowel. Anticancer Res 34(8):4153–4159
Saku T, Hayashi Y, Takahara O et al (1997) Salivary gland tumors among atomic bomb survivors, 1950–1987. Cancer 79(8):1465–1475
Sangiorgi C, Vallese D, Gnemmi I et al (2017) HSP60 activity on human bronchial epithelial cells. Int J Immunopathol Pharmacol 30(4):333–340
Schneider AB, Favus MJ, Stachura ME et al (1977) Salivary gland neoplasms as a late consequence of head and neck irradiation. Ann Intern Med 87(2):160
Scriven P, Coulson S, Haines R et al (2009) Activation and clinical significance of the unfolded protein response in breast cancer. Br J Cancer 101(10):1692–1698
Seethala RR, Stenman G (2017) Update from the 4th edition of the world health organization classification of head and neck tumours: tumors of the salivary gland. Head Neck Pathol 11(1):55–67
Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30
Spitz MR, Sider JG, Newell GR (1990) Salivary gland cancer and risk of subsequent skin cancer. Head Neck 12(3):254–256
Tabatabai S, Tafti M, Rafiei B (2015) Primary malignant epithelial salivary gland tumors in an Iranian population: a retrospective study of 81 cases. J Oral Maxillofac Pathol 19(1):47–52
To VSH, Chan JYW, Tsang RKY et al (2012) Review of salivary gland neoplasms. ISRN Otolaryngol. https://doi.org/10.5402/2012/872982
Trenkić Božinović M, Krasić D, Katić V et al (2015) A retrospective review of 139 major and minor salivary gland tumors. Med Glas 12(1):73–78
Wang G, Gu X, Chen L et al (2013) Comparison of the expression of 5 heat shock proteins in benign and malignant salivary gland tumor tissues. Oncol Lett 5(4):1363–1369
Yamaguchi M, Abiko Y, Nishimura M et al (2004) An immunohistochemical study of the localization of inducible nitric oxide synthase (iNOS) and heat shock protein (HSP) in pleomorphic adenoma. Acta Histochem Cytochem 37(4):267–271
Zhang J, Jiang Y, Jia Z et al (2007) Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer. Clin Exp Metastasis 23(7–8):401–410
Acknowledgements
A.J.L.M, and E.C. de M. were partially supported by IMET. This work was done under the agreement between IEMEST (Italy) and IMET (USA). This is the IMET contribution number: IMET 20-005.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors report no conflict of interest.
Ethical approval for studies involving animals
This article does not contain any studies with animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Basset, C.A., Cappello, F., Rappa, F. et al. Molecular chaperones in tumors of salivary glands. J Mol Hist 51, 109–115 (2020). https://doi.org/10.1007/s10735-020-09871-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-020-09871-y