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Mitochondrial transfer from Adipose stem cells to breast cancer cells drives multi-drug resistance Published: 14 June 2024
Background
Breast cancer (BC) is the second most prevalent cancer in the female population worldwide. The treatment algorithm of both early and advanced BC still includes chemotherapy in many therapeutic settings. However, many patients do not respond due to primary or acquired resistance.
BC cells (BCCs) are surrounded by mammary adipose tissue and intermingled with a repertoire of stromal cells such as adipose stem cells (ASCs), mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs) with endothelial and immune cells, constituting BC microenvironment (BCME), deeply influencing disease development, progression and treatment response. Interestingly, the adipose component is altered in BC patients, due to strong immune cells infiltration and chronic inflammatory status. MSCs/ASCs play a dominant role in reshaping BCME, promoting epithelial-to-mesenchymal transition (EMT) and supporting cancer stem cells (CSCs), which are, in turn, associated with multi-drug resistance (MDR). The role of ASCs in MDR was highlighted in a recent study where breast adipose tissue-derived ASCs showed a higher potential to enrich CSCs in BC, that, in turn, led to drug resistance.
Cancer cells and MSCs/ASCs can communicate through several mechanisms, such as tunneling nanotubes (TNTs), cell–cell fusion and extracellular vesicles (EVs) trafficking. These enable cells to exchange various intra-cellular components, including macro-molecules, organelles, vesicles, proteins, calcium ions and others.
Materials and methods (urval)
Cells and cell cultures
MCF-7, MDA-MB.231 and hASC52telo hTERT cells were purchased from ATCC. The naturally immortalized BC cell line BCAHC-1 was donated by the Pharmacology Department of the University of Calabria. MCF-7 and MDA-MB.231 cells were cultured in DMEM with glutamine, penicillin, streptomycin, and fetal bovine serum (FBS). BCAHC-1 cells were cultured in DMEM/F‐12 with FBS. hASC hTERT were cultured in Mesenchymal Stem Cell Basal Medium for Adipose-derived MSCs (ATCC) with Mesenchymal Stem Cell Growth Kit for Adipose-derived MSCs (ATCC, Manassas, Virginia). For hypoxia condition, where expected, we treated the cells with Cobalt Chloride (CoCl2) 100uM (Merck, Milan Italy). All cell lines were kept at 37 °C in a humidified atmosphere with 5% CO2 under mycoplasma-free conditions (checked every three months).
Digital holographic microscopy
For kinetic dose–response assay, a Holomonitor M4 microscope (Phase Holographic Imaging AB, Lund, Sweden) was used. Cells were seeded at a density of 104 cells/well and then subjected to MCP before treatment with DOX (1 µM for MDA-MB.231; 2 µM for MCF-7). Cells were continuously monitored for 24 h, in time-lapse mode (every hour), at multiple positions in each well using a high-precision motorized stage. The Holomonitor App suite cell imaging software was used for image analysis, for the evaluation of the cell viability parameters (cell density = #cells/cm2; percentage of confluence = %confluence). The results are showed as changes relative to zero time-point, from each area and presented as mean ± SE for all the monitored areas in each well. The assay has been performed three times in triplicate.
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Raderahttps://www.researchgate.net/publication/381444846_Mitochondrial_transfer_from_Adipose_stem_cells_to_breast_cancer_cells_drives_multi-drug_resistance
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SvaraRaderahttps://www.linkedin.com/posts/spencer-knight_celltherapy-genetherapy-biotech-activity-7209509361449119745-3W3q?utm_source=share&utm_medium=member_android
https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03087-8
SvaraRaderahttps://www.umft.ro/wp-content/uploads/2024/06/Carte-abstracte-Medis-2024.pdf
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