Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end‐products‐dependent manner

Oral squamous cell carcinoma (OSCC) affects approximately 30,000 people and is associated with tobacco use. Little is known about the mechanistic effects of second‐hand smoke in the development of OSSC. The receptor for advanced glycation end‐products (RAGE) is a surface receptor that is upregulated by second‐hand smoke and inhibited by semi‐synthetic glycosaminoglycan ethers (SAGEs). Our objective was to determine the role of RAGE during cigarette smoke extract‐induced cellular responses and to use SAGEs as a modulating factor of Ca9‐22 OSCC cell invasion. Ca9‐22 cells were cultured in the presence or absence of cigarette smoke extract and SAGEs. Cell invasion was determined and cells were lysed for western blot analysis. Ras and nuclear factor of kappa light polypeptide gene enhancer in B‐cells (NF‐κB) activation were determined. Treatment of cells with cigarette smoke extract resulted in: (i) increased invasion of OSCC; (ii) increased RAGE expression; (iii) inhibition of cigarette smoke extract‐induced OSCC cell invasion by SAGEs; (iv) increased Ras, increased AKT and NF‐κB activation, and downregulation by SAGEs; and (v) increased expression of matrix metalloproteinases (MMPs) 2, 9, and 14, and downregulation by SAGEs. We conclude that cigarette smoke extract increases invasion of OSCC cells in a RAGE‐dependent manner. Inhibition of RAGE decreases the levels of its signaling molecules, which results in blocking the cigarette smoke extract‐induced invasion.     

Laser ionization mass spectrometry in oral squamous cell carcinoma

Biomarker research in oral squamous cell carcinoma (OSCC) aims for screening/early diagnosis and in predicting its recurrence, metastasis and overall prognosis. This article reviews the current molecular perspectives and diagnosis of oral cancer with proteomics using matrix‐assisted laser desorption ionization (MALDI) and surface‐enhanced laser desorption ionization (SELDI) mass spectrometry (MS). This method shows higher sensitivity, accuracy, reproducibility and ability to handle complex tissues and biological fluid samples. However, the data interpretation tools of contemporary mass spectrometry still warrant further improvement. Based on the data available with laser‐based mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug targets. Majority of these biomarkers are involved in cell homeostasis and are either physiologic responders or enzymes. Therefore, proteins directly related to tumorigenesis have more diagnostic value. Salivary secretory markers are another group that offers a favourable and easy strategy for non‐invasive screening and early diagnosis in oral cancer. Key molecular inter‐related pathways in oral carcinogenesis are also intensely researched with software analysis to facilitate targeted drug therapeutics. The review suggested the need for incorporating ‘multiple MS or tandem approaches’ and focusing on a ‘group of biomarkers’ instead of single protein entities, for making early diagnosis and treatment for oral cancer a reality.     

MicroRNA‐137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

Oral lichen planus (OLP) is a common oral mucosal disease, which is generally considered a potentially malignant lesion. To identify efficiently prognostic biomarker, we investigated the microRNA‐137 (miR‐137) promoter methylation in OLP and compared with the samples from healthy volunteers and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR‐137 promoter methylation analysis using methylation‐specific PCR (MSP). To address the malignancy prediction potential from miR‐137 promoter methylation status, methylation of the p16 gene, a well‐known tumor suppressor, was investigated in the same samples. The p16 methylation and miR‐137 promoter methylation were found to be 25% and 35% in patients with OLP, 50% and 58.3% in patients with OSCC, and 0% and 0% in healthy subjects, respectively. The differences between miR‐137 and p16 methylation levels were statistically significant between healthy controls and patients. Methylation levels of the two promoters were also influenced by age, gender, and lesion duration. Interestingly, aberrant promoter methylation of the p16 and miR‐137 genes was only found in the epithelium but not in the connective tissue from patients with OLP. This raises the possibility to use miR‐137 methylation as a biomarker for malignant prediction in patients with OLP.     

The role of NEFL in cell growth and invasion in head and neck squamous cell carcinoma cell lines

The neurofilament light polypeptide (NEFL) gene located on chromosome 8q21 is associated with the cancer of several organs and is regarded as a potential tumor suppressor gene. However, the role of the NEFL protein has not yet been studied in cancer cells. Although evidence suggests that there is a correlation between NEFL expression and cancer, studies regarding the role of the NEFL protein have been mostly limited to neurological diseases, such as Charcot–Marie–Tooth's disease (CMT). Most of these studies have not explored the role of NEFL in cancer cell apoptosis and/or invasion. In this study, NEFL expression was manipulated, and apoptosis and invasion were compared in head and neck squamous cell carcinoma cell lines. The results show that the expression of NEFL induces cancer cell apoptosis and inhibits invasion in these cell lines, suggesting that NEFL may play a role in cancer cell apoptosis and invasion.     

口腔鳞癌脉管侵袭的研究

对４４例口腔鳞癌组织切片用抗血型抗原ＡＢＨ抗体作免疫组化染色，以研究癌组织对脉管的侵袭。结果表明，该方法为脉管内皮细胞提供了清晰的染色，显示脉管侵袭的阳性率为４０．９％，显著高于以Ｈ·Ｅ染色显示的阳性率（２０．５％）。口腔鳞癌组织侵袭脉管与其分化程度、生长方式及淋巴结转移有密切关系。作者提示口腔鳞癌脉管侵袭的研究对判断预后有重要意义