Conditioned medium of the osteosarcoma cell line U2OS induces hBMSCs to exhibit characteristics of carcinoma-associated fibroblasts via activation of IL-6/STAT3 signalling

2020 ◽  
Vol 168 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Longshuai Lin ◽  
Kai Huang ◽  
Weihong Guo ◽  
Chenghao Zhou ◽  
Gangyang Wang ◽  
...  

Abstract As a research hotspot in recent years, bone mesenchymal stem cells (BMSCs) play an important role in the process of a variety of human diseases, including cancers. However, in osteosarcoma, the role of BMSCs and their communication with tumour cells are not clear. In this study, we validated the communication of osteosarcoma (OS) cells with BMSCs. The results showed that the conditioned medium of osteosarcoma cell line U2OS (U2OS-CM) induces the carcinoma-associated fibroblasts (CAFs)-like transformation of BMSCs and promotes the proliferation, migration and invasion of BMSCs. Mechanistically, treatment of human bone mesenchymal stem cells (hBMSCs) with U2OS-CM results in a significant increase in the IL-6 expression and phosphorylation of STAT3. Furthermore, blockade of the IL-6/STAT3 signalling in hBMSCs rescues the transformation of CAF phenotype induced by U2OS-CM. And, human IL-6 can directly increase the expression of the CAF marker genes in hMSCs. Meanwhile, IL-6/STAT3 signalling involves in promoting effects of U2OS-CM on the proliferation, migration and invasion of BMSCs. In summary, our results suggest that BMSCs communicate with OS cells through IL-6/STAT3 signalling and play an important role in the progress of osteosarcoma.

2014 ◽  
Vol 8 (1) ◽  
pp. 127-132 ◽  
Author(s):  
PENG ZHANG ◽  
LING DONG ◽  
HUA LONG ◽  
TONG-TAO YANG ◽  
YONG ZHOU ◽  
...  

Author(s):  
Katayoun Bahman Soufiani ◽  
Ali Akbar Pourfathollah ◽  
Mahin Nikougoftar Zarifi ◽  
Ehsan Arefian

Conditioned medium (CM) derived from mesenchymal stem cells (MSCs) contains bioactive molecules including microRNAs (miRs) that could be a potential tool for controlling cancer cells' behavior. Due to the properties of CM, this study assesses the effects of miR-34a related MSCCM on tumor behavior through the evaluation of migration, invasion, apoptosis, and PDL1 expression in breast cancer cell lines. The miR-34a overexpression vector or scramble control was produced using lentiviral vectors, DNA cloning, and the transfection of the HEK-293 T cell line. It was then transduced into human adipose-derived mesenchymal stem cells (hAD-MSCs). MSC-CMs were collected and added onto MDA-MB-231 cell lines. The functional evaluations were performed by transwell, wound healing, and Annexin V/PI methods on the treated MDA-MB-231 cell lines. The PDL1 expression was also assessed by Real-time PCR and western blot. The findings of this study showed that ectopic miR-34a expression was significantly upregulated in manipulated hASC with miR-34a (p<0.0001). Treatment of MDA-MB-231 cell line with miR-34a-hAD-MSC-CM, scramble-hAD-MSC-CM, or hAD-MSC-CM displayed not only a reduction in the number of migrated or invaded cells (p=0.01) but also an increase in the apoptotic cells in the test group (p=0.02) when compared to the control groups. It also showed down-regulation in the gene (p=0.05) and protein expression levels of PDL1 in the test group. The results of the present study showed that simultaneous application of miR-34a and MSCCM can be considered as a new method for changing the cancerous microenvironment; and therefore, as a potential strategy in breast cancer therapy.


2020 ◽  
pp. 1-13
Author(s):  
Lu Deng ◽  
Chang Wang ◽  
Chao He ◽  
Li Chen

OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. METHODS: BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. RESULTS: EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. CONCLUSION: BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.


2018 ◽  
Vol 45 (6) ◽  
pp. 1653-1662 ◽  
Author(s):  
Pavani Koka ◽  
Reddy Sailaja Mundre ◽  
Rohini Rangarajan ◽  
Yamini Chandramohan ◽  
Raghunandha Kumar Subramanian ◽  
...  

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S330
Author(s):  
J. Costa-Rodrigues⁎ ◽  
C.A. Teixeira ◽  
M.H. Fernandes

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