The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC). Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples. Results: MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-beta 1 (TGF-beta 1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-beta 1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells. Conclusions: The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-beta 1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.Peer reviewe

The Response of Phagocytes Indoor Air Toxicity

This perspective presents a viewpoint on potential methods assessing toxicity of indoor air. Until recently, the major techniques to document moldy environment have been microbial isolation using conventional culture techniques for fungi and bacteria as well as in some instances polymerase chain reaction to detect microbial genetic components. However, it has become increasingly evident that bacterial and fungal toxins, their metabolic products, and volatile organic substances emitted from corrupted constructions are the major health risks. Here, we illustrate how phagocytes, especially neutrophils can be used as a toxicological probe. Neutrophils can be used either in vitro as probe cells, directly exposed to the toxic agent studied, or they can act as in vivo indicators of the whole biological system exposed to the agent. There are two convenient methods assessing the responses, one is to measure chemiluminescence emission from activated phagocytes and the other is to measure quantitatively by flow cytometry the expression of complement and immunoglobulin receptors on the phagocyte surface