Head and neck squamous cell carcinoma (HNSCC) is a world-wide malignancy. This study aimed to identify differential gene expression associated with the progression of disease from primary to metastatic HNSCC. Microdissection retrieved pure epithelial cells from paired primary tumours and cervical lymph node metastasis. cDNA microarray analysis and algorithm grouping identified differential mRNA expression of 301 genes. Quantitative reverse transcription-polymerase chain reaction analysis clarified the up-regulation of CCL19, CR2, EGR2, FUCA1, RGS1, and SELL, as well as the down-regulation of IGFBP6 and KLK8 in nodal metastasis compared to primary tumours. Immunohistochemistry confirmed the up-regulation of SELL and down-regulation of IGFBP6 in nodal metastasis relative to primary tumours. Interestingly, primary tumours exhibiting higher FUCA1 and SELL expression were associated with significantly worse patient survival. In OECM-1 HNSCC cells, inhibition of proliferation, migration, and anchorage-independent growth was noted following knockdown of SELL expression. In SAS HNSCC cells, expression of exogenous SELL resulted in increased invasion, anchorage-independent growth, and xenographic tumourigenesis in nude mice. Knockdown of FUCA1 and treatment with IGFBP6 inhibited the migration of OECM-1 cells. Knockdown of RGS1 inhibited the anchorage-independent growth of SAS cells. Our results provide a useful gene signature profile describing the factors underlying the metastasis of HNSCC to cervical lymph nodes, which may be beneficial for the treatment of HNSCC metastasis.

Head and neck squamous cell carcinoma (HNSCC) is a global malignancy. The insulin-like growth factor (IGF) signalling axis plays a critical role in tumourigenesis. This study defined the clinical and functional roles of insulin-like growth factor binding protein-5 (IGFBP-5) in HNSCC. Down-regulation of IGFBP-5 mRNA expression was found during the progression from pre-cancer to HNSCC. The down-regulation in HNSCC was associated with a higher propensity to nodal metastasis. SAS and OECM-1 are HNSCC cells that do, or do not, express IGFBP-5, respectively. Recombinant IGFBP-5 reduced the proliferation of OECM-1 cells and this was exerted mainly through blockade of the IGF pathways. Either IGFBP-5 or IGF-I treatment alone promoted OECM-1 migration, but a combination of treatments generated antagonistic effects. Overexpression of IGFBP-5 reduced the proliferation and anchorage-independent growth of both OECM-1 and SAS cells. Conversely, knockdown of IGFBP-5 expression significantly induced the proliferation and anchorage-independent growth of SAS cells. It also induced the growth of xenografted SAS tumours. SAS transfectants that expressed mutant or truncated IGFBP-5, which lack IGF binding activity, exhibited significantly lower anchorage-independent growth than vector control. This suggests that IGFBP-5 possesses an IGF-independent suppressor function. The suppressive effects of IGFBP-5 on the tumourigenesis of HNSCC might be invaluable to future neoplastic intervention.

MMP-13 could be a potential tumor marker for OSCC. The effects of EGCG in tumor inhibition may act partially through the modulation of MMP-13.

The areca nut extract-mediated activation of MMP-9 in gingival epithelial cells could signify a potential periodontal pathogenesis in areca chewers. The areca nut extract-mediated inhibition of cell viability and migration, together with the changed aggregation in gingival epithelial cells, suggests that impairment of the re-epithelization underlies the process and this, in turn, might exacerbate gingival inflammation.

This nested case-control study evaluated the role of polymorphisms in the myeloperoxidase (MPO) and catechol-O-methyltransferase (COMT) genes that modulate oxidative stress in breast cancer risk in a Chinese population. Our results demonstrate that the MPO A/A genotype was associated with a reduced risk of breast cancer (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.11-3.76), whereas there was no overall association of COMT genotype with breast cancer. Of note, an elevated breast cancer risk associated with the increasing numbers of high-risk genotypes of MPO and COMT genes was observed in women with a longer duration between menarche and first full-term pregnancy.