Transfer of metastatic traits via miR‐200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I

Tang, Dongdong; Xu, Xiaojuan; Ying, Jialiang; Xie, Tian; Cao, Gang

doi:10.1002/ctm2.139

Cited by 19 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extensive research has revealed that EVs are widely spread and can steadily exist in various body fluids including plasma, milk, and saliva [ 8 , 9 ]. Easy access to EVs and its wide existence ensure EVs to be a potent biomarker and imply its regulatory roles in diseases including tumors, autoimmune and inflammatory diseases [ 10 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

et al. 2021

View full text Add to dashboard Cite

Crohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

show abstract

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In line with our observations, a previous study reported that exosomes derived from 5-fluorouracil-resistant cells transferred p-STAT3 and conferred drug resistance to drug-sensitive cells [ 81 ]. Other studies demonstrated the extracellular vesicle/exosome-mediated metastatic properties of the bladder [ 64 ] and colorectal [ 82 ] cancers. Our findings partially elucidated the mechanism through which GSCs confer stemness and invasive properties to non-GSCs by cargo conveyer of oncogenic Akt, mTOR, PI3K, and activated STAT3 (p-STAT3).…”

Section: Discussionmentioning

confidence: 99%

A Preclinical Investigation of GBM-N019 as a Potential Inhibitor of Glioblastoma via Exosomal mTOR/CDK6/STAT3 Signaling

Huang

Wen

et al. 2021

Cells

View full text Add to dashboard Cite

Glioblastoma (GBM) is one of the most aggressive brain malignancies with high incidences of developing treatment resistance, resulting in poor prognoses. Glioma stem cell (GSC)-derived exosomes are important players that contribute to GBM tumorigenesis and aggressive properties. Herein, we investigated the inhibitory roles of GBM-N019, a novel small molecule on the transfer of aggressive and invasive properties through the delivery of oncogene-loaded exosomes from GSCs to naïve and non-GSCs. Our results indicated that GBM-N019 significantly downregulated the expressions of the mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and cyclin-dependent kinase 6 (CDK6) signaling networks with concomitant inhibitory activities against viability, clonogenicity, and migratory abilities of U251 and U87MG cells. Treatments with GBM-N019 halted the exosomal transfer of protein kinase B (Akt), mTOR, p-mTOR, and Ras-related protein RAB27A to the naïve U251 and U87MG cells, and rescued the cells from invasive and stemness properties that were associated with activation of these oncogenes. GBM-N019 also synergized with and enhanced the anti-GBM activities of palbociclib in vitro and in vivo. In conclusion, our results suggested that GBM-N019 possesses good translational relevance as a potential anti-glioblastoma drug candidate worthy of consideration for clinical trials against recurrent glioblastomas.

show abstract

“…The main role of EVs also includes their fusion with macrophages and other immune cells [ 30 , 31 ]. CSCs and their EVs are able to modulate cancer cell proliferation by the release of proteins [ 44 , 45 , 46 ] and miRNAs [ 30 , 47 , 48 , 49 , 50 , 51 ]. Examples are increasing, with results in favor or against cancer.…”

Section: Cscs and Their Evs Are Essential For Cancer Initiation And Its Processesmentioning

confidence: 99%

“…The first of these are in favor. The miR-92/PD-L1 pathway contributes to the suppression of immune cell function [ 30 ] and miR-200c stimulates the metastatic traits in colorectal cancer [ 47 ]. On the other hand, human liver cancer is attenuated in vitro and in vivo by miR-145 and miR-200 [ 48 ]; inhibition of lung metastasis is induced in osteosarcoma by miR-101 [ 49 ]; miR-8063 inhibits self renewal of GSC [ 50 ]; miR-663 inhibits the CSCs of a glioma [ 51 ]; and miR-1468-5p promotes a tumor immune escape [ 52 ].…”

Section: Cscs and Their Evs Are Essential For Cancer Initiation And Its Processesmentioning

confidence: 99%

“…The cancer role of MSCs has also been investigated via molecules (proteins, lipids, miRNAs), most often released from the EV cargoes. Identification of miRNAs active at one or more steps of MSC signaling cascades [ 59 , 60 , 61 , 62 ], and which are different from those involved in CSC action [ 47 , 48 , 49 , 50 , 51 ] were already established some years ago. Recent findings have led to the identification not only of miRs but also of signaling cascades they contribute to in order to activate.…”

Section: Role Of Mscs and Msc-evsmentioning

confidence: 99%

See 1 more Smart Citation

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Meldolesi

2022

IJMS

View full text Add to dashboard Cite

Stem cells, identified several decades ago, started to attract interest at the end of the nineties when families of mesenchymal stem cells (MSCs), concentrated in the stroma of most organs, were found to participate in the therapy of many diseases. In cancer, however, stem cells of high importance are specific to another family, the cancer stem cells (CSCs). This comprehensive review is focused on the role and the mechanisms of CSCs and of their specific extracellular vesicles (EVs), which are composed of both exosomes and ectosomes. Compared to non-stem (normal) cancer cells, CSCs exist in small populations that are preferentially distributed to the niches, such as minor specific tissue sites corresponding to the stroma of non-cancer tissues. At niches and marginal sites of other cancer masses, the tissue exhibits peculiar properties that are typical of the tumor microenvironment (TME) of cancers. The extracellular matrix (ECM) includes components different from non-cancer tissues. CSCs and their EVs, in addition to effects analogous to those of MSCs/EVs, participate in processes of key importance, specific to cancer: generation of distinct cell subtypes, proliferation, differentiation, progression, formation of metastases, immune and therapy resistance, cancer relapse. Many of these, and other, effects require CSC cooperation with surrounding cells, especially MSCs. Filtered non-cancer cells, especially macrophages and fibroblasts, contribute to collaborative cancer transition/integration processes. Therapy developments are mentioned as ongoing preclinical initiatives. The preliminary state of clinical medicine is presented in terms of both industrial development and future treatments. The latter will be administered to specific patients together with known drugs, with the aim of eradicating their tumor growth and metastases.

show abstract

Transfer of metastatic traits via miR‐200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I

Cited by 19 publications

References 45 publications

Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

A Preclinical Investigation of GBM-N019 as a Potential Inhibitor of Glioblastoma via Exosomal mTOR/CDK6/STAT3 Signaling

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Contact Info

Product

Resources

About