Acidic microenvironment induction of interleukin-8 expression and matrix metalloproteinase-2/-9 activation via acid-sensing ion channel 1 promotes breast cancer cell progression.

The cancer microenvironment exhibits local acidosis compared with the surrounding normal tissue. Many reports have shown that acidosis accelerates the invasiveness and metastasis of cancer, yet the underlying molecular mechanisms remain unclear. In the present study, we focused on acid-induced functional changes through acid receptors in breast cancer cells. Acidic treatment induced interleukin (IL)-8 expression in MDA-MB-231 cells and promoted cell migration and invasion. The acidic microenvironment elevated matrix metalloproteinase (MMP)-2 and MMP-9 activity, and addition of IL-8 had similar effects. However, inhibition of IL-8 suppressed the acid-induced migration and invasion of MDA-MB-231 cells. MDA-MB-231 cells express various acid receptors including ion channels and G protein-coupled receptors. Interestingly, acidic stimulation increased the expression of acid-sensing ion channel 1 (ASIC1), and acid-induced IL-8 was significantly decreased by ASIC1 knockdown. Moreover, phosphorylation of nuclear factor (NF)-κB was induced by acidic treatment, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that IL-8 induction by an acidic microenvironment promotes breast cancer development and that ASIC1 might be a novel therapeutic target for breast cancer metastasis.

Multi-body dynamics modelling of seated human body under exposure to whole-body vibration.

In vehicle systems occupational drivers might expose themselves to vibration for a long time. This may cause illness of the spine such as chronic lumbago or low back pain. Therefore, it is necessary to evaluate the influence of vibration to the spinal column and to make up appropriate guidelines or counter plans. In ISO2631-1 or ISO2631-5 assessment of vibration effects to human in the view of adverse-health effect was already presented. However, it is necessary to carry out further research to understand the effect of vibration to human body to examine their validity and to prepare for the future revision. This paper shows the detail measurement of human response to vibration, and the modelling of the seated human body for the assessment of the vibration risk. The vibration transmissibilities from the seat surface to the spinal column and to the head are measured during the exposure to vertical excitation. The modal paramters of seated subject are extracted in order to understand the dominant natural modes. For the evaluation of adverse-health effect the multi-body modelling of the spinal column is introduced. A simplified model having 10 DOFs is counstructed so that the transmissibilities of the model fit to those of experiment. The transient response analysis is illustrated when a half-sine input is applied. The relative displacements of vertebrae are evaluated, which can be a basis for the assessment of vibration risk. It is suggested that the multi-body dynamic model is used to evaluate the vibration effect to the spinal column for seated subjects.