The inhibition of aromatase alters the mechanical and rheological properties of non-small-cell lung cancer cell lines affecting cell migration.

Tumor invasion and metastasis are key aspects of non-small cell lung cancer (NSCLC). During migration, cells undergo mechanical alterations. The mechanical phenotype of breast cancer cells is correlated with aromatase gene expression. We have previously shown that targeting aromatase is a promising strategy for NSCLC. The aim of this study was to examine morphological and mechanical changes of NSCLC cells, upon treatment with aromatase inhibitor and correlate their ability to migrate and invade. In vitro experiments were performed using H23 and A549 NSCLC cell lines and exemestane was used for aromatase inhibition. We demonstrated that exemestane reduced H23 cell migration and invasion and caused changes in cell morphology including increased vacuolar structures and greater pleomorphism. In addition, exemestane changed the distribution of α-tubulin in H23 and A549 cells in a way that might destabilize microtubules polymerization. These effects were associated with increased cell viscosity and decreased elastic shear modulus. Although exemestane caused similar effects in A549 cells regarding viscosity and elastic shear modulus, it did not affect A549 cell migration and caused an increase in invasion. The increased invasion was in line with vimentin perinuclear localization. Our data show that the treatment of NSCLC cells with an aromatase inhibitor not only affects cell migration and invasion but also alters the mechanical properties of the cells. It suggests that the different origin of cancer cells is associated with different morphological characteristics and mechanical behavior.

Unveiling the longitudinal association between short sleep duration and the incidence of obesity: the Penn State Cohort.

OBJECTIVE: Several epidemiologic, longitudinal studies have reported that short sleep duration is a risk factor for the incidence of obesity. However, the vast majority of these studies used self-reported measures of sleep duration and did not examine the role of objective short sleep duration, subjective sleep disturbances and emotional stress. DESIGN: Longitudinal, population-based study. SUBJECTS: We studied a random sample of 815 non-obese adults from the Penn State Cohort in the sleep laboratory for one night using polysomnography (PSG) and followed them up for a mean of 7.5 years. Subjective and objective measures of sleep as well as emotional stress were obtained at baseline. Obesity was defined as a body mass index (BMI) ≥30 kg/ m(-2). RESULTS: The incidence of obesity was 15% and it was significantly higher in women and in individuals who reported sleep disturbances, shorter sleep duration and higher emotional stress. Significant mediating effects showed that individuals with subjective sleep disturbances who developed obesity reported the shortest sleep duration and the highest emotional stress, and that subjective sleep disturbances and emotional stress were independent predictors of incident obesity. Further analyses revealed that the association between short sleep duration, subjective sleep disturbances and emotional stress with incident obesity was stronger in young and middle-age adults. Objective short sleep duration was not associated with a significantly increased risk of incident obesity. CONCLUSION: Self-reported short sleep duration in non-obese individuals at risk of developing obesity is a surrogate marker of emotional stress and subjective sleep disturbances. Objective short sleep duration is not associated with a significant increased risk of incident obesity. The detection and treatment of sleep disturbances and emotional stress should become a target of our preventive strategies against obesity.