Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial–Mesenchymal Transition

Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to date, the mechanism of EMT induction remains to be fully elucidated. Recent findings in the field of intercellular communication have shed new light on this process and indicate the need for further studies into this important mechanism. New evidence supports the hypothesis that intercellular communication between mesenchymal stroma/stem cells (MSCs) and resident epithelial cells plays an important role in EMT induction. Besides direct interactions between cells, indirect paracrine interactions by soluble factors and extracellular vesicles also occur. Extracellular vesicles (EVs) are important mediators of intercellular communication, through the transfer of biologically active molecules, genetic material (mRNA, microRNA, siRNA, DNA), and EMT inducers to the target cells, which are capable of reprogramming recipient cells. In this review, we discuss the role of intercellular communication by EVs to induce EMT and the acquisition of stemness properties by normal and tumor epithelial cells.

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Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

Current Molecular Medicine ◽

10.2174/1566524020666200825163512 ◽

2020 ◽

Vol 20 ◽

Author(s):

Qionghui Wu ◽

Haidong Wei ◽

Wenbo Meng ◽

Xiaodong Xie ◽

Zhenchang Zhang ◽

...

Keyword(s):

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Epithelial Mesenchymal Transition ◽

Main Role ◽

Tumor Cell Adhesion ◽

Mesenchymal Transition ◽

Calcium Dependent ◽

Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

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Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00914.2018 ◽

2019 ◽

Vol 127 (2) ◽

pp. 645-653 ◽

Cited By ~ 1

Author(s):

Ivan J. Vechetti

Keyword(s):

Skeletal Muscle ◽

Extracellular Vesicles ◽

Human Body ◽

Intercellular Communication ◽

Skeletal Muscle Mass ◽

Genetic Material ◽

Muscle Adaptation ◽

Pathological Conditions ◽

Isolation Methods

Extracellular vesicles (EVs) were initially characterized as “garbage bags” with the purpose of removing unwanted material from cells. It is now becoming clear that EVs mediate intercellular communication between distant cells through a transfer of genetic material, a process important to the systemic adaptation in physiological and pathological conditions. Although speculative, it has been suggested that the majority of EVs that make it into the bloodstream would be coming from skeletal muscle, since it is one of the largest organs in the human body. Although it is well established that skeletal muscle secretes peptides (currently known as myokines) into the bloodstream, the notion that skeletal muscle releases EVs is in its infancy. Besides intercellular communication and systemic adaptation, EV release could represent the mechanism by which muscle adapts to certain stimuli. This review summarizes the current understanding of EV biology and biogenesis and current isolation methods and briefly discusses the possible role EVs have in regulating skeletal muscle mass.

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The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis

Cancers ◽

10.3390/cancers11040434 ◽

2019 ◽

Vol 11 (4) ◽

pp. 434 ◽

Cited By ~ 22

Author(s):

Wenjuan Mei ◽

Xiaozeng Lin ◽

Anil Kapoor ◽

Yan Gu ◽

Kuncheng Zhao ◽

...

Keyword(s):

Prostate Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Epithelial Mesenchymal Transition ◽

Critical Role ◽

Current Evidence ◽

Target Cells ◽

Mesenchymal Transition ◽

Prostate Cancer Stem Cells

Research in the last decade has clearly revealed a critical role of prostate cancer stem cells (PCSCs) in prostate cancer (PC). Prostate stem cells (PSCs) reside in both basal and luminal layers, and are the target cells of oncogenic transformation, suggesting a role of PCSCs in PC initiation. Mutations in PTEN, TP53, and RB1 commonly occur in PC, particularly in metastasis and castration-resistant PC. The loss of PTEN together with Ras activation induces partial epithelial–mesenchymal transition (EMT), which is a major mechanism that confers plasticity to cancer stem cells (CSCs) and PCSCs, which contributes to metastasis. While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs. TP53 and RB1 suppress lineage plasticity through the inhibition of SOX2 expression. In this review, we will discuss the current evidence supporting a major role of PCSCs in PC initiation and metastasis, as well as the underlying mechanisms regulating PCSCs. These discussions will be developed along with the cancer stem cell (CSC) knowledge in other cancer types.

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Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells

International Journal of Molecular Medicine ◽

10.3892/ijmm.2014.1935 ◽

2014 ◽

Vol 34 (5) ◽

pp. 1381-1387 ◽

Cited By ~ 17

Author(s):

JIALIN PAN ◽

JUHONG ZHANG ◽

XINGWEI ZHANG ◽

XI ZHOU ◽

SHENGYUE LU ◽

...

Keyword(s):

Angiotensin Ii ◽

Epithelial Cells ◽

Epithelial Mesenchymal Transition ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Mesenchymal Transition ◽

Renal Tubular

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The Role of the ERK Signaling Pathway on High Glucose-Induced Epithelial-Mesenchymal Transition in Cultured Human Renal Tubular Epithelial Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2018.1758 ◽

2018 ◽

Vol 8 (3) ◽

pp. 405-409

Author(s):

Jian-Rong Zhao ◽

Shan-Shan Xu ◽

Qin Dong ◽

Dong-Ying Shi

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

High Glucose ◽

Epithelial Mesenchymal Transition ◽

Erk Signaling ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Mesenchymal Transition ◽

Renal Tubular

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Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A

Tumor Biology ◽

10.1007/s13277-015-3711-9 ◽

2015 ◽

Vol 36 (12) ◽

pp. 9649-9659 ◽

Cited By ~ 9

Author(s):

Octavio Galindo-Hernandez ◽

Cristina Gonzales-Vazquez ◽

Pedro Cortes-Reynosa ◽

Emmanuel Reyes-Uribe ◽

Sonia Chavez-Ocaña ◽

...

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Extracellular Vesicles ◽

Epithelial Mesenchymal Transition ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Mesenchymal Transition

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TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00163.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. L525-L534 ◽

Cited By ~ 602

Author(s):

Brigham C. Willis ◽

Zea Borok

Keyword(s):

Epithelial Cells ◽

Lung Disease ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Critical Role ◽

Alveolar Epithelial Cells ◽

Mesenchymal Transition ◽

Fibrotic Lung Disease

Epithelial-mesenchymal transition (EMT), a process whereby fully differentiated epithelial cells undergo transition to a mesenchymal phenotype giving rise to fibroblasts and myofibroblasts, is increasingly recognized as playing an important role in repair and scar formation following epithelial injury. The extent to which this process contributes to fibrosis following injury in the lung is a subject of active investigation. Recently, it was demonstrated that transforming growth factor (TGF)-β induces EMT in alveolar epithelial cells (AEC) in vitro and in vivo, and epithelial and mesenchymal markers have been colocalized to hyperplastic type II (AT2) cells in lung tissue from patients with idiopathic pulmonary fibrosis (IPF), suggesting that AEC may exhibit extreme plasticity and serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. In this review, we describe the characteristic features of EMT and its mechanistic underpinnings. We further describe the contribution of EMT to fibrosis in adult tissues following injury, focusing especially on the critical role of TGF-β and its downstream mediators in this process. Finally, we highlight recent descriptions of EMT in the lung and the potential implications of this process for the treatment of fibrotic lung disease. Treatment for fibrosis of the lung in diseases such as IPF has heretofore focused largely on amelioration of potential inciting processes such as inflammation. It is hoped that this review will stimulate further consideration of the cellular mechanisms of fibrogenesis in the lung and especially the role of the epithelium in this process, potentially leading to innovative avenues of investigation and treatment.

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