Extracellular vesicles extracted from bone marrow mesenchymal stem cells carrying MicroRNA-342-3p inhibit the INHBA/IL13Rα2 axis to suppress the growth and metastasis of breast cancer

Liu, Qi; Zhang, Jing; Liu, Yi; Peng, Hai; Ying-qi, WU

doi:10.1016/j.tranon.2021.101333

Cited by 5 publications

(4 citation statements)

References 28 publications

(29 reference statements)

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“…We demonstrated rapid EV internalization by pancreatic cell lines, but each cell line exhibited different kinetics from the others. The rapid internalization of MSC-derived EVs, in vitro and in vivo, was also observed in different cell types, including leukemia cells [18,28], breast cancer cells [29] and glioblastoma cells [30].…”

Section: Discussionmentioning

confidence: 84%

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells

Draguet

Dubois

Bouland

et al. 2023

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Treatment of PDAC remains a major challenge. This study aims to evaluate, in vitro, the use of human umbilical cord mesenchymal stromal cell (UC-MSC)-derived EVs to specifically target pancreatic cancer cells. EVs were isolated from the FBS-free supernatants of the cultured UC-MSCs by ultracentrifugation and characterized by several methods. EVs were loaded with scramble or KRASG12D-targeting siRNA by electroporation. The effects of control and loaded EVs on different cell types were evaluated by assessing cell proliferation, viability, apoptosis and migration. Later, the ability of EVs to function as a drug delivery system for doxorubicin (DOXO), a chemotherapeutic drug, was also evaluated. Loaded EVs exhibited different kinetic rates of uptake by three cell lines, namely, BxPC-3 cells (pancreatic cancer cell line expressing KRASwt), LS180 cells (colorectal cell line expressing KRASG12D) and PANC-1 cells (pancreatic cell line expressing KRASG12D). A significant decrease in the relative expression of the KRASG12D gene after incubation with KRAS siRNA EVs was observed by real-time PCR. KRASG12D siRNA EVs significantly reduced the proliferation, viability and migration of the KRASG12D cell lines compared to scramble siRNA EVs. An endogenous EV production method was applied to obtain DOXO-loaded EVs. Briefly, UC-MSCs were treated with DOXO. After 24 h, UC-MSCs released DOXO-loaded EVs. DOXO-loaded EVs were rapidly taken up by PANC-1 cells and induced apoptotic cell death more efficiently than free DOXO. In conclusion, the use of UC-MSC-derived EVs as a drug delivery system for siRNAs or drugs could be a promising approach for the targeted treatment of PDAC.

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Section: Discussionmentioning

confidence: 84%

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells

Draguet

Dubois

Bouland

et al. 2023

Cancers

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“…axis in cancerous cells and inhibit metastasis by delivering miR-342-3p. 139 Katakowski and colleagues have shown that exosomes harvested from the BM-MSCs transfected with the miR-146b coding plasmid contain functional miR-146b and can be utilized as a vector for antitumor miRNA delivery. The researchers have reported that intratumoral administration of exosomes obtained from miR-146-expressing MSCs to a primary brain tumor rat model can inhibit glioma xenograft progression.…”

Section: Msc As a Therapeutic Vector For Suicide Gene Therapymentioning

confidence: 99%

“…Liu et al have reported that BM‐MSCs release extracellular vesicles (EVs) enriched with miR‐342‐3p. These EVs could suppress breast cancer growth by downregulating the INHBA/IL13Rα2 axis in cancerous cells and inhibit metastasis by delivering miR‐342‐3p 139 . Katakowski and colleagues have shown that exosomes harvested from the BM‐MSCs transfected with the miR‐146b coding plasmid contain functional miR‐146b and can be utilized as a vector for antitumor miRNA delivery.…”

Section: Various Application Of Mscs In Modern Cancer Therapy Approachesmentioning

confidence: 99%

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Taheri,

Tehrani,

Dehghani

et al. 2024

Medicinal Research Reviews

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Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

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“…MiR-342-3p uploaded in MSC exosomes not only inhibited metastasis and chemoresistance of BC cells by targeting ID4, 99 but also by inhibiting INHBA/IL13Rα2 axis. 100 Exosomal miRNA-551b-3p from BMSCs suppressed BC progression by modulating TRIM31/Akt signaling. 101 MiR-1236 carried by ADSC exosomes promoted the resistance response of BC cells to cisplatin, specifically involving two distinct mechanisms related to SLC9A1 downregulation and Wnt/β-linked protein inactivation.…”

Section: Drug Delivery Based On Stem Cell-derived Exosomesmentioning

confidence: 99%

The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications

Li,

He,

et al. 2023

BCTT

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Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20-23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

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Extracellular vesicles extracted from bone marrow mesenchymal stem cells carrying MicroRNA-342-3p inhibit the INHBA/IL13Rα2 axis to suppress the growth and metastasis of breast cancer

Abstract: Highlights BMSC-EVs carrying miR-342-3p could prevent breast cancer growth and metastasis by downregulating the INHBA/IL13Rα2 axis, highlighting a potential target for anti-cancer treatment for breast cancer.

Cited by 5 publications

References 28 publications

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications

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