Salivary Leptin as a Candidate Diagnostic Marker in Salivary Gland Tumors

Abstract

Background: Since the discovery of autonomous leptin production in salivary glands, very few studies have reported on the physiological or pathological meaning of this particular cytokine in saliva. The aim of this study was to investigate the expression of leptin and its receptors Ob-Ra and Ob-Rb in parotid salivary gland tumors, with particular regard to a potential use of leptin as a tumor marker. Methods: Parotid tissue samples from healthy individuals (n = 31) and tumor patients (n = 97, including tissue samples from pleomorphic adenomas, adenolymphomas, basal cell adenomas, and diverse carcinomas) were analyzed by use of ApoTome-technique microscopy, immunohistochemistry, immunofluorescence, immunoblotting, and quantitative real-time PCR. Salivary and plasma leptin concentrations were measured by using ELISA. Ultrasound was used to determine tumor size before surgery. Results: In all salivary gland tumors leptin was expressed in much higher amounts than in healthy parotid tissues. The cytokine was not imported from the blood but actively produced by the tumors. Immunoblotting results indicated that leptin was present as oligomers in salivary glands. Furthermore, the examined tumors overexpressed the receptor isoforms Ob-Ra and Ob-Rb. Measured leptin concentrations in mixed saliva samples were significantly increased in patients with parotid tumors [mean (SD) 673 (484) pg/mL in pleomorphic adenomas, 679 (465) pg/mL in adenolymphomas, and 880 (618) pg/mL in carcinomas] vs controls [125 (36) pg/mL] (P < 0.001). Conclusions: This is the first study to show that the analysis of salivary leptin in mixed saliva samples may allow preoperative differentiation between tumor patients and healthy individuals.

Evaluation of salivary adiponectin profile in obese patients

“…In addition, it has been reported that, under insulin resistance state, the increase of basement membrane permeability allows an enlarged passage of serum molecules [10]. Furthermore, the increase of salivary adiponectin expression could represent a biologic mechanism to counteract the sustained local inflammatory/infective state typical of obesity [9,24,25]. In fact, it is widely known that obese patients undergo frequent oral infection [24].…”

“…Furthermore, the increase of salivary adiponectin expression could represent a biologic mechanism to counteract the sustained local inflammatory/infective state typical of obesity [9,24,25]. In fact, it is widely known that obese patients undergo frequent oral infection [24]. On the other hand, to date there are no data about the expression of the T-cadherin receptor, the suggested depot of adiponectin in salivary cells as well as in physiopathological metabolic conditions; in this scenario, we cannot exclude that an altered expression of T-cadherin could be involved in the regulation of adiponectin levels in saliva of obese patients.…”

“…Adiponectin is produced as a monomer of 28 kDa that, through several post-translational modifications, self-assemblies as oligomers of different molecular weight: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) [6,13,18]. There is a great interest about the oligomeric state of adiponectin since it affects its biological activity [24]. In particular, in vitro studies revealed HMW as the most biologically active oligomers while in vitro studies demonstrated that HMW are more strongly associated with metabolic disorders representing a very useful diagnostic marker [12].…”

A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer

“…Chen et al [22] described elevated salivary levels of CA 125 in patients with ovarian cancer. Schapher et al [23] also suggested that salivary leptin was expressed in much higher amount in salivary gland tumors than in healthy parotid tissue. It has been reported that gastric cancer can also be identified at an early stage by using saliva proteome analysis [24].…”

Cytoplasmic and nuclear leptin expression in lacrimal gland tumours: a pilot study

“…Leptin acts as a growth factor for gastric and colorectal carcinomas as well as chondrosarcomas, and enhances the metastasis of these cancers 11–14. Recently, increased tissue leptin messenger RNA (mRNA) and leptin concentrations in breast and salivary gland tumours were reported 15 16. Indeed, salivary leptin was suggested as a diagnostic marker in salivary gland tumours 15.…”