Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation

Exosomes can transmit microRNAs (miRNAs) and other substances between different cells. Bone marrow mesenchymal stem cells (BMSCs) can migrate to tumor sites. They are related to a variety of tumors, but the role of miR-126-3p exosomes derived from BMSCs in gastric cancer has not been elucidated. miR-126-3p overexpressing BMSCs were established and cell supernatant exosomes were collected followed by measuring miR-126-3p level by PCR, ESM1 expression by western blot, targeting relationship by dual luciferase gene reporter assay along with analysis of cell proliferation, invasion and apoptosis. The addition of BMSCs exosomes to gastric cancer cells reduced the miR-126-3p level, promoted ESM1 expression, and worsened the biological behaviors of tumor cells. miR-126-3p-overexpressed BMSCs exosomes promoted miR-126-3p expression, resulting in the decrease of ESM1 expression and inhibiting the further deterioration. In conclusion, BMSCs can inhibit the increase of miR-126-3p expression and ESM1 to inhibit the deterioration of biological behaviors of gastric cancer cells.

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Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽

10.1038/s41388-021-01722-8 ◽

2021 ◽

Vol 40 (12) ◽

pp. 2296-2308

Author(s):

Mei Wang ◽

Xinxin Zhao ◽

Rong Qiu ◽

Zheng Gong ◽

Feng Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Cells ◽

Node Metastasis ◽

Signaling Activation

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

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Bone marrow-derived mesenchymal stem cells increase drug resistance in CD133-expressing gastric cancer cells by regulating the PI3K/AKT pathway

Tumor Biology ◽

10.1007/s13277-016-5319-0 ◽

2016 ◽

Vol 37 (11) ◽

pp. 14637-14651 ◽

Cited By ~ 5

Author(s):

Nuo Ji ◽

Ji-Wei Yu ◽

Xiao-Chun Ni ◽

Ju-Gang Wu ◽

Shou-Lian Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Drug Resistance ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Akt Pathway ◽

Gastric Cancer Cells ◽

Increase Drug Resistance

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Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2900 ◽

2022 ◽

Vol 12 (2) ◽

pp. 273-278

Author(s):

Daqing Jiang ◽

Xianxin Xie ◽

Cong Wang ◽

Weijie Li ◽

Jianjun He

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Marrow Mesenchymal Stem Cells ◽

Induced Apoptosis ◽

Signaling Activation

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

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The role of mmu-miR-155-5p-NF-κB signaling in the education of bone marrow-derived mesenchymal stem cells by gastric cancer cells

Cancer Medicine ◽

10.1002/cam4.1355 ◽

2018 ◽

Vol 7 (3) ◽

pp. 856-868 ◽

Cited By ~ 5

Author(s):

Mei Wang ◽

Fang Yang ◽

Rong Qiu ◽

Mengchu Zhu ◽

Huiling Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Gastric Cancer Cells

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Human Bone Marrow Mesenchymal Stem Cells Promote Gastric Cancer Growth via Regulating c-Myc

Stem Cells International ◽

10.1155/2018/9501747 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Bin Chen ◽

Jing Yu ◽

Qianqian Wang ◽

Yuanyuan Zhao ◽

Li Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Clinical Application ◽

Human Bone ◽

Human Bone Marrow ◽

Cancer Growth ◽

Gastric Cancer Cells ◽

Marrow Mesenchymal Stem Cells

The clinical application of human bone marrow mesenchymal stem cells (hBM-MSCs) has generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering. However, safety concerns over hBM-MSCs limit their clinical application. In this study, we observed that hBM-MSC-conditioned medium (hBM-MSC-CM) promotes gastric cancer development via upregulation of c-Myc. Our results showed that c-Myc was upregulated in MGC-803 and BGC-823 cells after hBM-MSC-CM treatment. Moreover, we found that the c-Myc inhibitor JQ1 and c-Myc siRNA decreased the expression of c-Myc in hBM-MSC-CM-treated tumor cells in vitro. Additionally, hBM-MSC-CM enhanced the migration and glucose uptake of gastric cancer cells. In vivo studies showed that JQ1 inhibited hBM-MSC-CM-induced gastric cancer growth. These results indicated that hBM-MSC-CM induced gastric cancer growth via upregulation of c-Myc, which may be a potential risk factor and/or a therapeutic target for clinical applications.

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