Myofibroblasts from salivary gland adenoid cystic carcinomas promote cancer invasion by expressing MMP2 and CXCL12.

OBJECTIVES: Salivary gland adenoid cystic carcinoma (ACC) is one of the most common malignant tumours in the oral and maxillofacial region, and has high aggressive potential. Tumour and stroma interactions are critical in determining the biological characteristics of malignancy. The aim of this study was to investigate the presence of myofibroblasts and their roles in the invasive characteristics of ACC. METHODS AND RESULTS: Immunohistochemistry was used to detect the expression of vimentin (VIM), α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP2) and CD34 in ACCs and normal salivary gland controls. A significant difference in α-SMA expression was found between normal controls and ACCs, suggesting the presence of myofibroblasts in ACCs. Immunohistochemical staining also demonstrated higher MMP2 expression in the stroma of ACCs than in the controls (P < 0.001). Primary culture of myofibroblasts from one ACC showed great invasive activity, with high expression of MMP2 and C-X-C motif chemokine 12 (CXCL12) by reverse transcription polymerase chain reaction (RT-PCR) analysis. CONCLUSIONS: This study demonstrated the presence of myofibroblasts in ACC. Myofibroblasts might be related to the aggressive growth behaviour of ACC, owing to their high levels of expression of MMP2 and CXCL12.

A microfluidic-based multi-shear device for investigating the effects of low fluid-induced stresses on osteoblasts.

Interstitial fluid flow (IFF) within the extracellular matrix (ECM) produces low magnitude shear stresses on cells. Fluid flow-induced stress (FSS) plays an important role during tissue morphogenesis. To investigate the effect of low FSS generated by IFF on cells, we developed a microfluidic-based cell culture device that can generate multiple low shear stresses. By changing the length and width of the flow-in channels, different continuous low level shear stresses could be generated in individual cell culture chambers. Numerical calculations demonstrate uniform shear stress distributions of the major cell culture area of each chamber. This calculation is further confirmed by the wall shear stress curves. The effects of low FSS on MC3T3-E1 proliferation and differentiation were studied using this device. It was found that FSS ranging from 1.5 to 52.6 µPa promoted MC3T3-E1 proliferation and differentiation, but FSS over 412 µPa inhibited the proliferation and differentiation of MC3T3-E1 cells. FSS ranging from 1.5 to 52.6 µPa also increased the expression of Runx2, a key transcription factor regulating osteoblast differentiation. It is suggested that Runx2 might be an important regulator in low FSS-induced MC3T3-E1 differentiation. This device allows for detailed study of the effect of low FSS on the behaviors of cells; thus, it would be a useful tool for analysis of the effects of IFF-induced shear stresses on cells.