scholarly journals Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Fei Mi ◽  
Liansheng Gong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Invasion ◽  
Interleukin 6 ◽  
Critical Role ◽  
Response To Treatment ◽  
Signal Transducer ◽  
Stat3 Pathway

Mesenchymal stem cells (MSCs) interact with tumor cells and regulate tumorigenesis and metastasis. As one of the important components of the tumor microenvironment, MSC-secreted cytokines play a critical role in cancer development. However, whether and how bone marrow MSCs (BMSCs) and their secreted cytokines participate in hepatocellular carcinoma (HCC) progression, still remains largely unknown. In the present study, we first measured the concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM). Next, we assessed the changes of invasion ability in response to treatment of BMSC-CM or recombinant IL-6 in two human HCC cell lines Bel-7404 and HepG2. Then we analyzed the level of key components of the IL-6 signal pathway, including IL-6 receptor and signal transducer (i.e. IL-6R and gp130), a transcription factor STAT3 (signal transducer and activator of transcription 3), as well as its target genes BCL2, CCND1, MCL1 and MMP2, in BMSC-CM or recombinant IL-6 treated Bel-7404 and HepG2 cells. Results showed that a considerable amount of IL-6 was secreted by BMSCs, and BMSC-CM markedly elevated Bel-7404 cell invasion rate and stimulated the signal transduction of IL-6/STAT3 pathway. Neutralizing the secreted IL-6 bioactivity by the anti-IL-6 antibody diminished the invasion-promoting effect and down-regulated IL-6/STAT3 pathway of BMSC-CM treated Bel-7404 cells. In conclusion, we found that BMSCs may activate the IL-6/STAT3 signaling pathway and promote cell invasion in Bel-7404 cells, suggesting that this protumor effect should be seriously considered before clinical application of MSC-mediated cancer therapy.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Restrain the Malignant Behaviors of A549 Lung Cancer Cells Under Hypoxia via miR-145

2022 ◽  
Vol 12 (3) ◽  
pp. 597-601
Author(s):  
Haibin Song ◽  
Heng Zhang ◽  
Lei Li
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Invasion ◽  
A549 Cells ◽  
Hypoxia Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Lung Cancer Stem Cells

Deriving from bone marrow, the bone marrow mesenchymal stem cells (BMSCs) possess multipolar chemotaxis, proliferation potential, along with the capability to differentiate into various types of cells. Moreover, the hypoxic stimulation can effectively induce BMSCs differentiation. This study intends to explore the impediment of BMSCs on malignant behaviors of lung cancer stem cells under hypoxia. A co-culture system of BMSCs with A549 cells was established and then assigned into normoxia group, hypoxia group (50, 100, and 200 nmol/L) followed by analysis of cell viability by CCK-8 assay and miR-145 expression by qRT-PCR. In addition, A549 cells were grouped into NC group, miR-145-mimics group, and miR-145-inhibitors group followed by analysis of cell invasion and levels of miR-145 and Oct4. Hypoxia group exhibited a reduced cell viability and higher miR-145 expression (146.01±21.23%) compared to normoxia group (P < 0.05). Transfection of miR-145-mimic significantly upregulated miR-145 and decreased cell invasion (7.49±1.43%) compared with miR-145-inhibitors group or NC group (P < 0.05). Meanwhile, Oct4 level in miR-145-mimics group (0.934±2.98) was significantly decreased (P < 0.05). In conclusion, under hypoxia condition, the co-culture with BMSCs can upregulated miR-145 level, effectively reduce the viability of lung cancer stem cells and restrain proliferation capability.

scholarly journals Serum-mediated Activation of Bone Marrow–derived Mesenchymal Stem Cells in Ischemic Stroke Patients

2018 ◽  
Vol 27 (3) ◽  
pp. 485-500 ◽  
Author(s):  
Gyeong Joon Moon ◽  
Yeon Hee Cho ◽  
Dong Hee Kim ◽  
Ji Hee Sung ◽  
Jeong Pyo Son ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Critical Role ◽  
Trophic Factors ◽  
Human Mscs ◽  
Stroke Patients ◽  
Serum Factors ◽  
Control Serum

Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS). MSCs cultured in growth medium with 10% SS or NS exhibited higher proliferation indices than those cultured with FBS ( P < 0.01). FBS-, NS-, and SS-hMSCs showed differences in the expression of trophic factors; vascular endothelial growth factor, glial cell–derived neurotrophic factor, and fibroblast growth factor were densely expressed in samples cultured with SS ( P < 0.01). In addition, SS-MSCs revealed different cell cycle– or aging-associated messenger RNA expression in a later passage, and β-galactosidase staining showed the senescence of MSCs observed during culture expansion was lower in MSCs cultured with SS than those cultured with NS or FBS ( P < 0.01). Several proteins related to the activity of receptors, growth factors, and cytokines were more prevalent in the serum of stroke patients than in that of normal subjects. Neurogenesis and angiogenesis were markedly increased in rats that had received SS-MSCs ( P < 0.05), and these rats showed significant behavioral improvements ( P < 0.01). Our results indicate that stroke induces a process of recovery via the activation of MSCs. Culture methods for MSCs using SS obtained during the acute phase of a stroke could constitute a novel MSC activation method that is feasible and efficient for the neurorestoration of stroke.

Bone Marrow Mesenchymal Stem Cells Exhibit a Transdifferentiation and Therapeutic Effects in a Murine Model of Orthotopic Hepatocellular Carcinoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Tumor Diameter ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.

scholarly journals Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

2006 ◽  
Vol 191 (3) ◽  
pp. 715-725 ◽  
Author(s):  
Ana María Pino ◽  
Juan Manuel Rodríguez ◽  
Susana Ríos ◽  
Pablo Astudillo ◽  
Laura Leiva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Vitamin D ◽  
Mesenchymal Stem Cells ◽  
Critical Role ◽  
Tritiated Water ◽  
Cell Activity ◽  
Human Mesenchymal Stem Cells ◽  
Aromatase Activity ◽  
Water Release

Human mesenchymal stem cells (hMSCs) are multipotent cells present in bone marrow, which differentiate into osteoblasts and adipocytes, among other lineages. Oestrogens play a critical role in bone metabolism; its action may affect the adipocyte to osteoblast ratio in the bone marrow. In hMSCs, oestrogens are synthesized from C19 steroids by the enzyme aromatase cytochrome P450. In this study, we assessed whether aromatase enzymatic activity varied through early osteogenic (OS) and adipogenic (AD) differentiation. Also, we studied the effect of leptin and 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on aromatase cell activity. Finally, we analysed whether conditions that modify oestrogen generation by cells affected hMSCs differentiation. For these purposes, hMSCs derived from post-menopausal women (65–86 years old) were cultured under basal, OS or AD conditions, in the presence or the absence of leptin and 1,25(OH)2D3. Aromatase activity was measured by the tritiated water release assay and by direct measurement of steroids synthesized from 3H-labelled androstenedione or testosterone. Our results showed that different OS and AD patterns of aromatase activity developed during the first period of differentiation (up to 7 days). A massive and sharp surge of aromatase activity at 24 h characterized early OS differentiation, while increased but constant aromatase activity was increased through adipogenesis. Both leptin and vitamin D increased aromatase activity during osteogenesis, but not during adipogenesis; finally, we showed that favourable aromatase substrates concentration restrained MSCs adipogenesis but improved osteogenesis. Thus, it could be inferred that a high and early increase of local oestrogen concentration in hMSCs affects their commitment either restraining AD or facilitating OS differentiation, or both.

scholarly journals Interleukin-6 Knockout Inhibits Senescence of Bone Mesenchymal Stem Cells in High-Fat Diet-Induced Bone Loss

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujue Li ◽  
Lingyun Lu ◽  
Ying Xie ◽  
Xiang Chen ◽  
Li Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Interleukin 6 ◽  
High Fat Diet ◽  
Cell Senescence ◽  
Low Grade ◽  
High Fat ◽  
Bone Mesenchymal Stem Cells

Obesity, a chronic low-grade inflammatory state, not only promotes bone loss, but also accelerates cell senescence. However, little is known about the mechanisms that link obesity, bone loss, and cell senescence. Interleukin-6 (IL-6), a pivotal inflammatory mediator increased during obesity, is a candidate for promoting cell senescence and an important part of senescence-associated secretory phenotype (SASP). Here, wild type (WT) and (IL-6 KO) mice were fed with high-fat diet (HFD) for 12 weeks. The results showed IL-6 KO mice gain less weight on HFD than WT mice. HFD induced trabecular bone loss, enhanced expansion of bone marrow adipose tissue (BMAT), increased adipogenesis in bone marrow (BM), and reduced the bone formation in WT mice, but it failed to do so in IL-6 KO mice. Furthermore, IL-6 KO inhibited HFD-induced clone formation of bone marrow cells (BMCs), and expression of senescence markers (p53 and p21). IL-6 antibody inhibited the activation of STAT3 and the senescence of bone mesenchymal stem cells (BMSCs) from WT mice in vitro, while rescued IL-6 induced senescence of BMSCs from IL-6 KO mice through the STAT3/p53/p21 pathway. In summary, our data demonstrated that IL-6 KO may maintain the balance between osteogenesis and adipogenesis in BM, and restrain senescence of BMSCs in HFD-induced bone loss.

Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs)-Derived miR-200c Regulates Wingless-Related Integration Site (Wnt)/β-Catenin Signaling in Prostate Cancer by Targeting Cortactin (CTTN)

2022 ◽  
Vol 12 (1) ◽  
pp. 215-220
Author(s):  
Wei Chen ◽  
Juan Jiang ◽  
Yu Wang ◽  
Gang Feng ◽  
Yan Fei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signal Transduction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Invasion ◽  
Integration Site ◽  
Tumor Model ◽  
Enhance Tumor Growth

Bone marrow-derived mesenchymal stem cells (BMSCs) are an integral part of cancer microenvironment. We intend to clarify BMSC-derived exosomes’ role in prostate cancer. The exosomes miR-200c secreted by BMSCs were identified by electron microscopy. The mice tumor model was used to explore the role of miR-200c’s in tumor mice. Cell invasion was assessed by transwell assay and Wnt/β-catenin expression was measured by western blot. Exosomes miR-200c derived from BMSCs promoted tumor cell invasion and activated Wnt/β-catenin signaling. miR-200c targets CTTN-mediated cell signal transduction, and blocking CTTN expression can suppression miR-200c-mediated Wnt/β-catenin signal transduction and inhibit cell invasion. In conclusion, miR-200c regulates CTTN, thereby inducing Wnt/β-catenin signaling to enhance tumor growth.

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