Glucose Enhances Pro-Tumorigenic Functions of Mammary Adipose-Derived Mesenchymal Stromal/Stem Cells on Breast Cancer Cell Lines

Abstract

Adiposity and diabetes affect breast cancer (BC) progression. We addressed whether glucose may affect the interaction between mammary adipose tissue-derived mesenchymal stromal/stem cells (MAT-MSCs) and BC cells. Two-dimensional co-cultures and spheroids were established in 25 mM or 5.5 mM glucose (High Glucose-HG or Low Glucose-LG) by using MAT-MSCs and MCF7 or MDA-MB231 BC cells. Gene expression was measured by qPCR, while protein levels were measured by cytofluorimetry and ELISA. CD44high/CD24low BC stem-like sub-population was quantified by cytofluorimetry. An in vivo zebrafish model was assessed by injecting spheroid-derived labeled cells. MAT-MSCs co-cultured with BC cells showed an inflammatory/senescent phenotype with increased abundance of IL-6, IL-8, VEGF and p16INK4a, accompanied by altered levels of CDKN2A and LMNB1. BC cells reduced multipotency and increased fibrotic features modulating OCT4, SOX2, NANOG, αSMA and FAP in MAT-MSCs. Of note, these co-culture-mediated changes in MAT-MSCs were partially reverted in LG. Only in HG, MAT-MSCs increased CD44high/CD24low MCF7 sub-population and promoted their ability to form mammospheres. Injection in zebrafish embryos of HG spheroid-derived MCF7 and MAT-MSCs was followed by a significant cellular migration and caudal dissemination. Thus, MAT-MSCs enhance the aggressiveness of BC cells in a HG environment.

Targeting G-quadruplex motifs interferes with differentiation of adipose-derived mesenchymal stem cells

“…Next, we evaluated the effects of Braco-19 on pro-inflammatory molecules known or expected to be produced by ASCs and ADIPO [ 18 ]. Specifically, we chose molecules characterizing a senescence-associated secretory phenotype (SASP) to evaluate if their modulation could account for the slight reduction of LMNB1 observed (Fig.…”

The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

“…Increasing interest in the relationship between systemic metabolism, tumor metabolism, immunometabolism, and cancer outcomes, alongside evolving technologies expanding both the available data and the community's ability to mine it to develop new insights. To that end, in this study, we utilized multiple publicly available breast cancer datasets, including "ACRIN-FLT-Breast (ACRIN 6688)", TCGA BRCA "Phenotypes", TCGA BRCA "IlluminaHiSeq", "TCGA TARGET GTEx", "Node-negative breast cancer (Desmedt 2007)", "ICGC (donor centric)", As opposed to genes or metabolic fluxes involved in glucose [24][25][26][27][28][29][30][31]or lipid metabolism [31][32][33][34][35][36][37][38][39], there exists a relative paucity of studies exploring the impact of expression of genes regulating amino acid uptake in breast cancer. Therefore, we elected to focus the current study on the expression of LAT1, which transports large amino acids including leucine, isoleucine, valine, phenylalanine, methionine, tyrosine, histidine, and tryptophan into the cell, and its relationships with body weight, tumor cell proliferation, and immune infiltration.…”

Human Platelet-Rich Plasma Regulates Canine Mesenchymal Stem Cell Migration through Aquaporins

“…The presence of mineralization foci was demonstrated by Alizarin Red S staining (Sigma-Aldrich, St. Louis, MO, USA). Adipogenic differentiation was achieved as described in [ 21 ]. Differentiated cells were photographed by the Olimpus DP20 microscope digital camera system (Olympus Corporation, Tokyo, Japan).…”