Publications

Tumor secreted extracellular vesicles (EVs) are potent intercellular signaling platforms. They are responsible for the accommodation of the premetastatic niche (PMN) to support cancer cell engraftment and metastatic growth. However, complex cancer cell composition within the tumor increases also the heterogeneity among cancer secreted EVs subsets, a functional diversity that has been poorly explored. This phenomenon is particularly relevant in highly plastic and heterogenous triple-negative breast cancer (TNBC), in which a significant representation of malignant cancer stem cells (CSCs) is displayed. Herein, we selectively isolated and characterized EVs from CSC or differentiated cancer cells (DCC; EVsCSC and EVsDCC , respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVsCSC and EVsDCC contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVsDCC activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVsCSC promoted the activation of α-SMA+ myofibroblastic CAFs subpopulations and increased the endothelial remodeling, enhancing the invasive potential of TNBC cells in vitro and in vivo. In addition, solely the EVsCSC mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

JTD Keywords: chemoresistance, dormancy, drives, extracellular vesicles, invasion, plasticity, premetastatic niche, triple-negative breast cancer, tumor microenvironment, Cancer cell plasticity, Cell line, tumor, Extracellular vesicles, Fibroblasts, Humans, Lung, Neoplastic stem cells, Premetastatic niche, Triple negative breast neoplasms, Triple-negative breast cancer, Tumor microenvironment

[Figure: see text].

JTD Keywords: activation, cell extrusion, contraction, drives, homeostasis, interface, junctions, kinase, tension, Adhesion, Article, Cell membranes, Chemical activation, Cytology, E-cadherin, Epithelial monolayers, Epithelium, Homoeostasis, Human, Mechanical instabilities, Monolayers, Morphological transformations, Morphology, Normal tissue, Oncogenics, Soft substrates, Substrates, Tissue, Tissue mechanics, Tissue morphology, Tumor development

The poor rehabilitation success rate, including the cases of ineffective and detrimental adaptations, make stroke a leading cause of disability. Thus, it is essential to recognize the mechanisms driving healthy motor recovery to improve such rate. Stroke alters the Synergy Architecture (SA), the modular muscle control system. So SA analysis may constitute a powerful tool to design and assess rehabilitation procedures. However, current impairment scales do not consider the patient's neuromuscular state. To gain insights into this hypothesis, we recorded multiple myoelectric signals from upper-limb muscles, in healthy subjects, while executing a set of common rehabilitation exercises. We found that SA reveals optimized motor control strategies and the positive effects of the use of visual feedback (VF) on motor control. Furthermore we demonstrate that the right and left arm's SA share the basic structure within the same subject, so we propose using the unaffected limb's SA as a reference motion pattern to be reached through rehabilitation.

JTD Keywords: Bars, Electromyography, Motor drives, Neuromuscular, Vectors, Visualization