MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells

2017 ◽  
Vol 40 (5) ◽  
pp. 457-470 ◽  
Author(s):  
Katayoon Pakravan ◽  
Sadegh Babashah ◽  
Majid Sadeghizadeh ◽  
Seyed Javad Mowla ◽  
Majid Mossahebi-Mohammadi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Vegf Signaling ◽  
Signaling Axis ◽  
In Vitro Angiogenesis

scholarly journals Mesenchymal stem cell-derived extracellular vesicles may promote breast cancer cell dormancy

2018 ◽  
Vol 9 ◽  
pp. 204173141881009 ◽  
Author(s):  
Jake Casson ◽  
Owen G Davies ◽  
Carol-Anne Smith ◽  
Matthew J Dalby ◽  
Catherine C Berry
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Cell Dormancy

Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, while upregulating cell adhesion, thus retaining the cancer cells within the bone marrow microenvironment. Here, MCF7 breast cancer cells were treated with mesenchymal stem cell–derived extracellular vesicles, resulting in reduced migration in two-dimensional and three-dimensional culture, with reduced cell proliferation and enhanced adhesion, collectively supporting cancer cell dormancy.

scholarly journals Mesenchymal stem cell secretion of chemokines during differentiation into osteoblasts, and their potential role in mediating interactions with breast cancer cells

2009 ◽  
Vol 124 (2) ◽  
pp. 326-332 ◽  
Author(s):  
Alan P. Molloy ◽  
Fiachra T. Martin ◽  
Roisin M. Dwyer ◽  
Tomas P. Griffin ◽  
Mary Murphy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Potential Role ◽  
Cell Secretion

Mesenchymal stem cell-secreted extracellular vesicles instruct stepwise dedifferentiation of breast cancer cells into dormancy at the bone marrow perivascular region

2021 ◽  
pp. canres.CAN-20-2434-A.2020
Author(s):  
Oleta A. Sandiford ◽  
Robert J. Donnelly ◽  
Markos El-Far ◽  
Lisa M. Burgmeyer ◽  
Garima Sinha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells

scholarly journals Towards understanding cancer stem cell heterogeneity in the tumor microenvironment

2018 ◽  
Author(s):  
Federico Bocci ◽  
Larisa Gearhart-Serna ◽  
Marcelo Boareto ◽  
Mariana Ribeiro ◽  
Eshel Ben-Jacob ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Inflammatory Cytokines ◽  
Primary Tumor ◽  
Breast Cancer Cells

AbstractThe Epithelial-Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) formation are two paramount processes driving tumor progression, therapy resistance and cancer metastasis. Some recent experiments show that cells with varying EMT and CSC phenotypes are spatially segregated in the primary tumor. The underlying mechanisms generating such spatiotemporal dynamics and heterogeneity in the tumor micro-environment, however, remain largely unexplored. Here, we show through a mechanism-based dynamical model that the diffusion of EMT-inducing signals such as TGF-β in a tumor tissue, together with non-cell autonomous control of EMT and CSC decision-making via juxtacrine signaling mediated via the Notch signaling pathway, can explain experimentally observed disparate localization of subsets of CSCs with varying EMT states in the tumor. Our simulations show that the more mesenchymal CSCs lie at the invasive edge, while the hybrid epithelial/mesenchymal (E/M) CSCs reside in the tumor interior. Further, motivated by the role of Notch-Jagged signaling in mediating EMT and stemness, we investigated the microenvironmental factors that promote Notch-Jagged signaling. We show that many inflammatory cytokines that can promote Notch-Jagged signaling such as IL-6 can (a) stabilize a hybrid E/M phenotype, (b) increase the likelihood of spatial proximity of hybrid E/M cells, and (c) expand the fraction of CSCs. To validate the predicted connection between Notch-Jagged signaling and stemness, we knocked down JAG1 in hybrid E/M SUM149 human breast cancer cellsin vitro. JAG1 knockdown significantly restricted organoid formation, confirming the key role that Notch-Jagged signaling can play in tumor progression. Together, our integrated computational-experimental framework reveals the underlying principles of spatiotemporal dynamics of EMT and CSCs in the tumor microenvironment.Significance statementThe presence of heterogeneous subsets of cancer stem cells (CSCs) remains a clinical challenge. These subsets often occupy different regions in the primary tumor and have varied epithelial-mesenchymal phenotypes. Here, we device a theoretical framework to investigate how the tumor microenvironment (TME) modulates this spatial patterning. We find that a spatial gradient of EMT-inducing signal, coupled with juxtacrine Notch-JAG1 signaling triggered by inflammatory cytokines in TME, explains this spatial heterogeneity. Finally,in vitroJAG1 knockdown experiments in triple negative breast cancer cells severely restricts the growth of tumor organoid, hence validating the association between JAG1 and CSC fraction. Our results offer insights into principles of spatiotemporal patterning in TME, and identifies a relevant target to alleviate multiple CSC subsets – JAG1.

scholarly journals Adipose Mesenchymal Stem Cell-Derived Exosomal microRNA-1236 Reduces Resistance of Breast Cancer Cells to Cisplatin by Suppressing SLC9A1 and the Wnt/β-Catenin Signaling

2020 ◽  
Vol Volume 12 ◽  
pp. 8733-8744
Author(s):  
Zhongming Jia ◽  
Huamin Zhu ◽  
Hongguang Sun ◽  
Yitong Hua ◽  
Guoqiang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Exosomal Microrna

scholarly journals The FBXW2–MSX2–SOX2 axis regulates stem cell property and drug resistance of cancer cells

2019 ◽  
Vol 116 (41) ◽  
pp. 20528-20538 ◽  
Author(s):  
Yuan Yin ◽  
Chuan-Ming Xie ◽  
Hua Li ◽  
Mingjia Tan ◽  
Guoan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
E3 Ligase ◽  
Stem Cell Property ◽  
Sox2 Expression ◽  
Cell Property

SOX2 is a key transcription factor that plays critical roles in maintaining stem cell property and conferring drug resistance. However, the underlying mechanisms by which SOX2 level is precisely regulated remain elusive. Here we report that MLN4924, also known as pevonedistat, a small-molecule inhibitor of neddylation currently in phase II clinical trials, down-regulates SOX2 expression via causing accumulation of MSX2, a known transcription repressor of SOX2 expression. Mechanistic characterization revealed that MSX2 is a substrate of FBXW2 E3 ligase. FBXW2 binds to MSX2 and promotes MSX2 ubiquitylation and degradation. Likewise, FBXW2 overexpression shortens the protein half-life of MSX2, whereas FBXW2 knockdown extends it. We further identified hypoxia as a stress condition that induces VRK2 kinase to facilitate MSX2–FBXW2 binding and FBXW2-mediated MSX2 ubiquitylation and degradation, leading to SOX2 induction via derepression. Biologically, expression of FBXW2 or SOX2 promotes tumor sphere formation, which is blocked by MSX2 expression. By down-regulating SOX2 through inactivation of FBXW2 E3 ligase, MLN4924 sensitizes breast cancer cells to tamoxifen in both in vitro and in vivo cancer cell models. Thus, a negative cascade of the FBXW2–MSX2–SOX2 axis was established, which regulates stem cell property and drug resistance. Finally, an inverse correlation of expression was found between FBXW2 and MSX2 in lung and breast cancer tissues. Collectively, our study revealed an anticancer mechanism of MLN4924. By inactivating FBXW2, MLN4924 caused MSX2 accumulation to repress SOX2 expression, leading to suppression of stem cell property and sensitization of breast cancer cells to tamoxifen.

scholarly journals Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

2010 ◽  
Vol 184 (10) ◽  
pp. 5885-5894 ◽  
Author(s):  
Shyam A. Patel ◽  
Justin R. Meyer ◽  
Steven J. Greco ◽  
Kelly E. Corcoran ◽  
Margarette Bryan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Regulatory T Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells
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