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Authordc.contributor.authorPonce Calderón, Iván Emilio
Authordc.contributor.authorGarrido, Nelson
Authordc.contributor.authorTobar Bachler, Nicolás Andrés
Authordc.contributor.authorMelo, Francisco
Authordc.contributor.authorSmith, Patricio
Authordc.contributor.authorMartínez, Jorge
Cita de ítemdc.identifier.citationMetabolites 2021, 11, 432es_ES
Abstractdc.description.abstractBreast tumors belong to the type of desmoplastic lesion in which a stiffer tissue structure is a determinant of breast cancer progression and constitutes a risk factor for breast cancer development. It has been proposed that cancer-associated stromal cells (responsible for this fibrotic phenomenon) are able to metabolize glucose via lactate production, which supports the catabolic metabolism of cancer cells. The aim of this work was to investigate the possible functional link between these two processes. To measure the effect of matrix rigidity on metabolic determinations, we used compliant elastic polyacrylamide gels as a substrate material, to which matrix molecules were covalently linked. We evaluated metabolite transport in stromal cells using two different FRET (Fluorescence Resonance Energy Transfer) nanosensors specific for glucose and lactate. Cell migration/invasion was evaluated using Transwell devices. We show that increased stiffness stimulates lactate production and glucose uptake by mammary fibroblasts. This response was correlated with the expression of stromal glucose transporter Glut1 and monocarboxylate transporters MCT4. Moreover, mammary stromal cells cultured on stiff matrices generated soluble factors that stimulated epithelial breast migration in a stiffness-dependent manner. Using a normal breast stromal cell line, we found that a stiffer extracellular matrix favors the acquisition mechanistical properties that promote metabolic reprograming and also constitute a stimulus for epithelial motility. This new knowledge will help us to better understand the complex relationship between fibrosis, metabolic reprogramming, and cancer malignancy.es_ES
Patrocinadordc.description.sponsorshipComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1181168es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.uri*
Keywordsdc.subjectBreast canceres_ES
Keywordsdc.subjectMonocarboxylate transporterses_ES
Títulodc.titleMatrix stiffness modulates metabolic interaction between human stromal and breast cancer cells to stimulate epithelial motilityes_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Indexationuchile.indexArtículo de publícación WoSes_ES

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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States