Effects of hyaluronic acid and CD44 interaction on the proliferation and invasiveness of malignant pleural mesothelioma

Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25???g/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA?CCD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA?CCD44 interaction is a potentially useful therapeutic target in MPM.     

Epithelial–mesenchymal transition in cancer development and its clinical significance

The epithelial–mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009)     

Effect of highway driving on the health of factory workers

Commuting transportation is one of the important factors in the administration of safety management in industries. Most workers commute to work by car and are certain to make use of highways, mainly because of the special condition of factory locations. In this study, we investigated the effect of communicating by car on the health of factory workers. The proportion of males was significantly higher in the highway (HW) group than in the non-highway (NHW) group, and the former was younger than the latter. BMI, systolic blood pressure, diastolic blood pressure, and total cholesterol deteriorated significantly in the NHW group after 5-year periodic medical checkups. However, in the HW group, those factors did not change except for systolic blood pressure and significant improvements in triglyceride. The percentage of those who follow a good lifestyle regarding excise and nutrition, and have a solution for stress, was lower in the HW group than in the NHW group. Nevertheless, the percentage of those who did not feel stress was significantly higher in the HW group than in the NHW group, suggesting a stress-relieving effect of highway driving. Highway driving might have an unexpectedly good impact on the health of factory workers.     

Role of crosstalk between interleukin-6 and transforming growth factor-beta 1 in epithelial–mesenchymal transition and chemoresistance in biliary tract cancer

AimsThe mechanisms of progression in biliary tract cancer (BTC) with inflammation, including epithelial–mesenchymal transition (EMT), are not well understood. We focused on two inflammation-associated cytokines, interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1), and investigated their expression and activity, as well as their relationship to key features of malignancy, in tumour samples from patients with BTC and in cultured BTC cells.MethodsWe employed five BTC cell lines (MzChA-1, gemcitabine-resistant MzChA-1, HuCCT-1, KMCH and CCLP-1) to evaluate IL-6/TGF-β1 expression, tumour cell invasion, EMT and chemoresistance to gemcitabine in the presence or absence of recombinant human (rh) IL-6 and TGF-β1. Possible pathways were evaluated with specific pathway inhibitors and small interfering RNA (siRNA). We also used 20 resected specimens from patients with BTC to verify the results in vitro.ResultsIL-6 and TGF-β1 expression was associated with features of malignancy such as EMT and chemoresistance in the four BTC cell lines. Addition of rh IL-6 and TGF-β1 increased endogenous IL-6 and TGF-β1 expression through crosstalk and induced cell invasion, EMT and chemoresistance. Smad4 functioned in this process in a dominant manner, and inhibition by SMAD4 siRNA reduced IL-6 and TGF-β1 expression, blocked invasion, and reversed EMT and chemoresistance in cells exposed to rh IL-6 and TGF-β1 and in gemcitabine-resistant cells. Immunohistochemistry in resected specimens revealed IL6, TGF-β1, N-cadherin and Smad4 staining at the invasion front.ConclusionCrosstalk between IL-6 and TGF-β1 is associated with malignant features, including EMT, and Smad4 works in a dominant manner to promote these features.