No abstract

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.

Recent decades have seen a plethora of regenerating new tissues in order to treat a multitude of cardiovascular diseases. Autografts, xenografts and bioengineered extracellular matrices have been employed in this endeavor. However, current limitations of xenografts and exogenous scaffolds to acquire sustainable cell viability, anti-inflammatory and non-cytotoxic effects with anti-thrombogenic properties underline the requirement for alternative bioengineered scaffolds. Herein, we sought to encompass the methods of biofabricated scaffolds via 3D printing and bioprinting, the biomaterials and bioinks recruited to create biomimicked tissues of cardiac valves and vascular networks. Experimental and computational designing approaches have also been included. Moreover, the in vivo applications of the latest studies on the treatment of cardiovascular diseases have been compiled and rigorously discussed.

Cell biomechanics plays a major role as a promising biomarker for early cancer diagnosis and prognosis. In the present study, alterations in modulus of elasticity, cell membrane roughness, and migratory potential of MCF-7 (ER+) and SKBR-3 (HER2+) cancer cells were elucidated prior to and post treatment with conditioned medium from human umbilical mesenchymal stem cells (hUMSCs-CM) during static and dynamic cell culture. Moreover, the therapeutic potency of hUMSCs-CM on cancer cell’s viability, migratory potential, and F-actin quantified intensity was addressed in 2D surfaces and 3D scaffolds. Interestingly, alterations in ER+ cancer cells showed a positive effect of treatment upon limiting cell viability, motility, and potential for migration. Moreover, increased post treatment cell stiffness indicated rigid cancer cells with confined cell movement and cytoskeletal alterations with restricted lamellipodia formation, which enhanced these results. On the contrary, the cell viability and the migratory potential were not confined post treatment with hUMSCs-CM on HER2+ cells, possibly due to their intrinsic aggressiveness. The increased post treatment cell viability and the decreased cell stiffness indicated an increased potency for cell movement. Hence, the therapy had no efficacy on HER2+ cells.

The onset and progression of cancer are strongly associated with the dissipation of adhesion forces between cancer cells, thus facilitating their incessant attachment and detachment from the extracellular matrix (ECM) to move toward metastasis. During this process, cancer cells undergo mechanical stresses and respond to these stresses with membrane deformation while inducing protrusions to invade the surrounding tissues. Cellular response to mechanical forces is inherently related to the reorganization of the cytoskeleton, the dissipation of cell–cell junctions, and the adhesion to the surrounding ECM. Moreover, the role of focal adhesion proteins, and particularly the role of vinculin in cell attachment and detachment during migration, is critical, indicating the tight cell–ECM junctions, which favor or inhibit the metastatic cascade. The biomechanical analysis of these sequences of events may elucidate the tumor progression and the potential of cancer cells for migration and metastasis. In this work, we focused on the evaluation of the spreading rate and the estimation of the adhesion strength between breast cancer cells and ECM prior to and post-treatment with anti-tumor agents. Specifically, different tamoxifen concentrations were used for ER+ breast cancer cells, while even concentrations of trastuzumab and pertuzumab were used for HER2+ cells. Analysis of cell stiffness indicated an increased elastic Young’s modulus post-treatment in both MCF-7 and SKBR-3 cells. The results showed that the post-treatment spreading rate was significantly decreased in both types of breast cancer, suggesting a lower metastatic potential. Additionally, treated cells required greater adhesion forces to detach from the ECM, thus preventing detachment events of cancer cells from the ECM, and therefore, the probability of cell motility, migration, and metastasis was confined. Furthermore, post-detachment and post-treatment vinculin levels were increased, indicating tighter cell–ECM junctions, hence limiting the probability of cell detachment and, therefore, cell motility and migration.