Investigation of Roles of SLC38A1 in Proliferation and Differentiation of Mouse Tongue Epithelium and Expression in Human Oral Tongue Squamous Cell Carcinoma.

The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression of SLC38A1 and its regulation in human tongue oral squamous cell carcinoma (OTSCC). Employing Slc38a1 wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation of SLC38A1 mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of the SLC38A1 chromosomal locus or hypomethylation of the SLC38A1 promoter region might be important for the upregulation of SLC38A1 in OTSCC.

Salivary Biomarkers in Lung Cancer.

A very low percentage of lung cancer (LC) cases are discovered at an early and treatable stage of the disease, leading to an abysmally low 5-year survival rate. This underscores the immediate necessity for improved diagnostic, prognostic, and predictive biomarkers for LC. Biopsied lung tissue, blood, and plasma are common sources used for LC diagnosis and monitoring of the disease. A growing number of studies have reported saliva to be a useful biological sample for early and noninvasive detection of oral and systemic diseases. Nevertheless, salivary biomarker discovery remains underresearched. Here, we have compiled the available literature to provide an overview of the current understanding of salivary markers for LC detection and provided perspectives for future clinical significance. Valuable markers with diagnostic and prognostic potentials in LC have been discovered in saliva, including metabolic (catalase activity, triene conjugates, and Schiff bases), inflammatory (interleukin 10, C-X-C motif chemokine ligand 10), proteomic (haptoglobin, zinc-α-2-glycoprotein, and calprotectin), genomic (epidermal growth factor receptor), and microbial candidates (Veillonella and Streptococcus). In combination, with each other and with other established screening methods, these salivary markers could be useful for improving early detection of the disease and ultimately improve the survival odds of LC patients. The existing literature suggests that saliva is a promising biological sample for identification and validation of biomarkers in LC, but how saliva can be utilized most effectively in a clinical setting for LC management is still under investigation.

Response of human oral mucosal epithelial cells to different storage temperatures: A structural and transcriptional study.

PURPOSE: Seeking to improve the access to regenerative medicine, this study investigated the structural and transcriptional effects of storage temperature on human oral mucosal epithelial cells (OMECs). METHODS: Cells were stored at four different temperatures (4°C, 12°C, 24°C and 37°C) for two weeks. Then, the morphology, cell viability and differential gene expression were examined using light and scanning electron microscopy, trypan blue exclusion test and TaqMan gene expression array cards, respectively. RESULTS: Cells stored at 4°C had the most similar morphology to non-stored controls with the highest viability rate (58%), whereas the 37°C group was most dissimilar with no living cells. The genes involved in stress-induced growth arrest (GADD45B) and cell proliferation inhibition (TGFB2) were upregulated at 12°C and 24°C. Upregulation was also observed in multifunctional genes responsible for morphology, growth, adhesion and motility such as EFEMP1 (12°C) and EPHA4 (4°C-24°C). Among genes used as differentiation markers, PPARA and TP53 (along with its associated gene CDKN1A) were downregulated in all temperature conditions, whereas KRT1 and KRT10 were either unchanged (4°C) or downregulated (24°C and 12°C; and 24°C, respectively), except for upregulation at 12°C for KRT1. CONCLUSIONS: Cells stored at 12°C and 24°C were stressed, although the expression levels of some adhesion-, growth- and apoptosis-related genes were favourable. Collectively, this study suggests that 4°C is the optimal storage temperature for maintenance of structure, viability and function of OMECs after two weeks.

Loss of S100A14 expression at the tumor-invading front correlates with poor differentiation and worse prognosis in oral squamous cell carcinoma.

BACKGROUND: We previously showed a tumor-suppressive function of S100A14 in oral squamous cell carcinoma (OSCC). This study aimed to examine the prognostic significance and differentiation-related function of S100A14 in OSCC. METHODS: S100A14 expression was examined in 170 OSCCs from Norwegian and Nepalese populations using immunohistochemistry. Pro-differentiation function was investigated by overexpressing and silencing S100A14 expression in OSCC-derived cells. External transcriptomic datasets were used to validate association between S100A14 and differentiation markers in OSCC. RESULT: Loss of S100A14 expression at the invading tumor fronts significantly correlated with poor differentiation and reduced 10-years survival of OSCC-patients. Multivariate Cox analysis identified S100A14 to be an independent prognostic factor. Modulation of S100A14 expression in OSCC-derived cells positively correlated with the expression of differentiation markers. Analysis of external datasets supported the pro-differentiation function of S100A14. CONCLUSION: These results indicate that S100A14 is a pro-differentiation protein and its expression might be useful as a prognostic marker in OSCC.

Blood lactate dynamics in awake and anaesthetized mice after intraperitoneal and subcutaneous injections of lactate-sex matters.

Lactate treatment has shown a therapeutic potential for several neurological diseases, including Alzheimer's disease. In order to optimize the administration of lactate for studies in mouse models, we compared blood lactate dynamics after intraperitoneal (IP) and subcutaneous (SC) injections. We used the 5xFAD mouse model for familial Alzheimer's disease and performed the experiments in both awake and anaesthetized mice. Blood glucose was used as an indication of the hepatic conversion of lactate. In awake mice, both injection routes resulted in high blood lactate levels, mimicking levels reached during high-intensity training. In anaesthetized mice, SC injections resulted in significantly lower lactate levels compared to IP injections. Interestingly, we observed that awake males had significantly higher lactate levels than awake females, while the opposite sex difference was observed during anaesthesia. We did not find any significant difference between transgenic and wild-type mice and therefore believe that our results can be generalized to other mouse models. These results should be considered when planning experiments using lactate treatment in mice.