scholarly journals c-Kit-Positive Adipose Tissue-Derived Mesenchymal Stem Cells Promote the Growth and Angiogenesis of Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Wenjie Li ◽  
Haiqian Xu ◽  
Cheng Qian

Background. Adipose tissue-derived mesenchymal stem cells (ASCs) improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer.Methods. ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs) were isolated from Balb/c mice. c-Kit-positive (c-Kit+) or c-Kit-negative (c-Kit-) ASCs were cocultured with 4T1 breast cancer cells. Orthotropic murine models of 4T1, EPCs + 4T1, and c-Kit+/-ASCs + 4T1/EPCs were established in Balb/c mice.Results. In coculture, c-Kit+ASCs enhanced the viability and proliferation of 4T1 cells and stimulated c-Kit expression and interleukin-3 (IL-3) release. In mouse models, c-Kit+ASCs + 4T1/EPCs coinjection increased the tumor volume and vessel formation. Moreover, IL-3, stromal cell-derived factor-1, and vascular endothelial growth factor A in the c-Kit+ASCs + 4T1/EPCs coinjection group were higher than those in the 4T1, EPCs + 4T1, and c-Kit-ASCs + 4T1/EPCs groups.Conclusions. c-Kit+ASCs may promote breast cancer growth and angiogenesis by a synergistic effect of c-Kit and IL-3. Our findings suggest that c-Kit+subpopulations of ASCs should be eliminated in fat grafts for breast reconstruction of cancer patients following mastectomy.

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
RS Challapalli ◽  
RM Dwyer ◽  
N McInerney ◽  
MJ Kerin ◽  
AJ Lowery

Abstract Background Adipose-derived stem cells (ADSCs) are a promising cell source for adipose tissue engineering. Currently, novel breast reconstruction techniques using ADSCs are actively being explored. Systemic chemo- & hormonal therapy may impede tissue regeneration in breast cancer patients. However, the effect of hormonal therapy on ADSCs and their regenerative capabilities is poorly understood. Aims The current study aims to analyse the effect of Afimoxifene, an active metabolite of Tamoxifen, on proliferation and viability of ADSCs in vitro Method Lipoaspirates or adipose tissue were obtained with informed consent from breast cancer patients and healthy controls. The isolated ADSCs were subjected to single or multiple dose(s) of Z-4-Hydroxytamoxifen (12.5nM, 25nM, 50nM, 100nM and 1μM) and, analyzed on days 1, 3 and 5, using CellTitre 96 ® AQueous Cell proliferation assay. T47D and MDA-MB-231 cell lines were used as positive and negative controls, respectively. Result ADSCs were obtained from a total of 3 patients. ADSCs were isolated from a cancer patient with/without active disease at the time of sample procurement and healthy subjects opting for elective cosmetic procedures. Morphology, CFU assay and adipogenic differentiation assay were used to validate stem cell population. Afimoxifene demonstrated no statistically significant reduction in the viability or proliferation of the ADSCs, irrespective of the dose- or time-dependent exposure or cancer status (p >0.05). Conclusion Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration. Key words Adipose-derived stem cells, Afimoxifene, Breast reconstruction, Hormone therapy, Tamoxifen. Take-home message Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration


2010 ◽  
Vol 19 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Vinícius Bassaneze ◽  
Valério Garrone Barauna ◽  
Carolina Lavini-Ramos ◽  
Jorge Kalil ◽  
Isolmar Tadeu Schettert ◽  
...  

2010 ◽  
Vol 400 (4) ◽  
pp. 461-465 ◽  
Author(s):  
Masamitsu Konno ◽  
Tatsuo S. Hamazaki ◽  
Satsuki Fukuda ◽  
Makoto Tokuhara ◽  
Hideho Uchiyama ◽  
...  

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Biljana Ljujic ◽  
Marija Milovanovic ◽  
Vladislav Volarevic ◽  
Bridgid Murray ◽  
Diana Bugarski ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Mohsen Sheykhhasan ◽  
Naser Kalhor ◽  
Azar Sheikholeslami ◽  
Masoumeh Dolati ◽  
Elaheh Amini ◽  
...  

Background. Despite recent advances in scientific knowledge and clinical practice, management, and treatment of breast cancer, as one of the leading causes of female mortality, breast cancer remains a major burden. Recently, methods employing stem cells and their derivatives, i.e., exosomes, in gene-based therapies hold great promise. Since these natural nanovesicles are able to transmit crucial cellular information which can be engineered to have robust delivery and targeting capacity, they are considered one of the modes of intercellular communication. miR-145, one of the downregulated microRNAs (miRNAs) in various cancers, can regulate tumor cell invasion, metastasis, apoptosis, and proliferation and stem cell differentiation. Objectives. The aim of this study was to investigate the role of exosomes secreted from adipose tissue-derived mesenchymal stem cells (MSCs) for miR-145 transfection into breast cancer cells in order to weaken their expansion and metastasis. Methods. Here, we exploited the exosomes from adipose tissue-derived mesenchymal stem cells (MSC-Exo) to deliver miR-145 in the T-47D breast cancer cell line. Lentiviral vectors of miR-145-pLenti-III-enhanced green fluorescent protein (eGFP) and empty pLenti-III-eGFP as the backbone were used to transfect MSCs and T-47D cells. In order to find the efficiency of exosomes as a delivery vehicle, the expression level of some miR-145 target genes, including Rho-Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), Matrix Metalloproteinase 9 (MMP9), and Tumor Protein p53 (TP53), was compared in all treatment groups (T-47D cells treated by miR-145-transfected MSCs and their derivatives or their backbone) and control group (untransfected T-47D cells) using real-time PCR. Results. The obtained data represented the inhibitory effect of miR-145 on apoptosis induction and metastasis in both direct miR-treated groups. However, exosome-mediated delivery caused an improved anticancer property of miR-145. Conclusion. Restoration of miR-145 using MSC-Exo can be considered a potential novel therapeutic strategy in breast cancer in the future.


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