The interplay between adipose-derived stem cells and bladder cancer cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Maj M
PROVIDER: S-EPMC6181926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The bladder patch constructed with the bladder acellular matrix (BAM) and adipose-derived stem cells (ASCs) was incubated with the omentum for bladder reconstruction in a rat model of bladder augmentation cystoplasty. A self-designed perfusion system and five different decellularization protocols were used to prepare the BAM. Finally, an optimal protocol (group C) was screened out by comparing the cell nucleus residue, collagen structure preservation and biologically active components retention of the prepared BAM. ASCs-seeded (BAM-ASCs group) and unseeded BAM (BAM group) were incubated with the omentum for 7 days to promote neovascularization and then perform bladder reconstruction. Hematoxylin and eosin and Masson's trichrome staining indicated that the bladder patches in the BAM-ASCs group could better regenerate the bladder wall structure compared to the BAM group. Moreover, immunofluorescence analyses demonstrated that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels, and the physiological function (maximal bladder capacity, max pressure prior to voiding and bladder compliance) restoration in the BAM-ASCs group. The results demonstrated that the self-designed perfusion system could quickly and efficiently prepare the whole bladder scaffold and confirmed that the prepared BAM could be used as the scaffold material for functional bladder tissue engineering applications.
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Project description:Mesenchymal stem cells in tumor microenvironment can influence therapeutic responses in various types of cancers. For triple negative breast cancer, chemotherapy remains the mainstay of standard treatment. Our aim was to investigate the correlation between human adipose-derived stem cells (hAdSCs) and chemoresistance in triple negative breast cancer.Conditioned medium was collected from hAdSCs, which was isolated from breast cancer patients who had had breast mastectomy. The expression of selected CD markers was evaluated by flow cytometry to characterize hAdSCs. By array analyses of the secreted cytokines and chemokines of hAdSCs, we identified CXCL1 that mediated doxorubicin resistance and the expression of ATP-binding cassette transporters ABCG2 in TNBC. By microRNA microarray, the association between hAdSC-mediated doxorubicin resistance in TNBC was also revealed.Conditioned medium collected from hAdSCs elicited doxorubicin resistance and enhanced the expression of ABCG2, which is a transporter responsible for the efflux of doxorubicin. CXCL1 secreted by hAdSCs downregulated miR-106a expression in triple negative breast cancer, and resulted in ABCG2 upregulation and doxorubicin resistance.Our findings suggest that CXCL1 secreted by hAdSCs elicits doxorubicin resistance through miR-106a-mediated ABCG2 upregulation in triple negative breast cancer. These findings provide a better understanding of the importance of adipose-derived stem cells in breast cancer microenvironment regarding to the development of chemoresistance and reveal the potential of discovering novel therapeutic strategies to overcome drug resistance in TNBC.
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Project description:Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be "epithelial"-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727.
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