scholarly journals A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

2018 ◽  
Vol 19 (12) ◽  
pp. 3968 ◽  
Author(s):  
Enrico Spugnini ◽  
Mariantonia Logozzi ◽  
Rossella Di Raimo ◽  
Davide Mizzoni ◽  
Stefano Fais
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Mesenchymal Transition ◽  
Metastatic Cascade ◽  
Target Organs

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

scholarly journals Long non-coding RNAs and their role in metastasis

2019 ◽  
Vol 11 (2) ◽  
pp. 91-97
Author(s):  
Ozal Beylerli ◽  
Ilgiz F. Gareev ◽  
Aferin Beilerli
Keyword(s):  
Regulatory Networks ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Metastatic Cascade ◽  
Multistep Process ◽  
Non Coding Rnas ◽  
And Migration

Cancer metastasis is a multistep process in which cancer cells leave the primary focus, survive in the bloodstream, and colonize in a distant organ. This is the main cause of cancer morbidity and mortality. It is mediated by a multistep process called the metastatic cascade. Initial steps include local invasion and migration, angiogenesis, epithelial-mesenchymal transition (EMF) and intravasation. Non-coding RNAs represent a large part of the transcriptome, with long non-coding RNAs (lncRNAs) constituting a large proportion. The perception of long non-coding RNAs as fragments of RNA and transcriptional noise has been constantly replaced by their role as confirmed targets for various physiological processes in the past few years. A large amount of evidence has revealed their role at all stages of carcinogenesis and in modulating metastasis through regulatory networks. In this review, we focus on the role of long non-coding RNAs as promoters or inhibitors in the main stages of the metastatic cascade, and in particular consider their role in the metastasis of malignant tumors to the brain.

scholarly journals Role of Mesenchymal Stem Cells—Derived Exosomes in Osteoarthritis Treatment

2018 ◽  
Vol 62 (4) ◽  
pp. 19-23
Author(s):  
K. Huňáková ◽  
M. Hluchý ◽  
M. Kuricová ◽  
K. Ševčík ◽  
J. Rosocha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Bioactive Molecules ◽  
Main Role ◽  
Ribonucleic Acids ◽  
Mesenchymal Transition ◽  
Osteoarthritis Treatment ◽  
Cartilage Injuries

Abstract Exosomes are nanovesicles that are involved in inter-cellular communication and are secreted by many types of cells. Exosomes secreted by stem cells can effectively transport bioactive proteins, messenger ribonucleic acids (mRNAs) and microribonucleic acids (miRNAs) organelles and play important roles in intercellular communication and the regulation of tissue regeneration. This transfer of bioactive molecules plays a main role in: tumor invasion and metastasis, immune and inflammation modulation, epithelial-mesenchymal transition and neurobiology. Mesenchymal Stem Cells (MSC) exosomes provide new perspectives for the development of an off-the-shelf and cell-free MSC therapy for the treatment of cartilage injuries and osteoarthritis. This report describes the progress in exosome studies and potential clinical use for osteoarthritis treatment.

scholarly journals The emerging role of circular RNAs in common solid malignant tumors in children

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiabin Yu ◽  
Li Yang ◽  
Hongting Lu
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Circular Rnas ◽  
Development Research ◽  
Physical And Mental Health ◽  
Invasive Ability ◽  
Mesenchymal Transition ◽  
Circular Structure ◽  
Solid Malignant Tumors

AbstractMalignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.

scholarly journals Therapeutic Targeting of Epithelial Plasticity Programs: Focus on the Epithelial-Mesenchymal Transition

2017 ◽  
Vol 203 (2) ◽  
pp. 114-127 ◽  
Author(s):  
Reem Malek ◽  
Hailun Wang ◽  
Kekoa Taparra ◽  
Phuoc T. Tran
Keyword(s):  
Cancer Cells ◽  
Regulatory Networks ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Therapeutic Targets ◽  
Treatment Resistance ◽  
Mesenchymal Transition ◽  
Epithelial Plasticity ◽  
Canonical Pathways

Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer. In this review we organized our discussion on pathways and agents that can be used to target the EMT in cancer into 3 groups: (1) extracellular inducers of EMT, (2) the transcription factors that orchestrate the EMT transcriptome, and (3) the downstream effectors of EMT. We highlight only briefly specific canonical pathways known to be involved in EMT, such as the signal transduction pathways TGFβ, EFGR, and Axl-Gas6. We emphasize in more detail pathways that we believe are emerging novel pathways and therapeutic targets such as epigenetic therapies, glycosylation pathways, and immunotherapy. The heterogeneity of tumors and the dynamic nature of epithelial plasticity in cancer cells make it likely that targeting only 1 EMT-related process will be unsuccessful or only transiently successful. We suggest that with greater understanding of epithelial plasticity regulation, such as with the EMT, a more systematic targeting of multiple EMT regulatory networks will be the best path forward to improve cancer outcomes.

scholarly journals N-cadherin in cancer dormancy

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Garima Sinha ◽  
Pranela Rameshwar
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Signaling Cascades ◽  
Intercellular Interaction ◽  
Adhesion Protein ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Cancer Dormancy ◽  
Rho Family

AbstractN-cadherin is an adhesion protein, which is important for intercellular interaction. It is involved in cell migration and motility during embryonic development, neuronal synapsis and cancer metastasis. There are several signaling cascades affected by N-cadherin including TGF-β, Rho family. N-cadherin is associated at the cytoplasmic domain with catenins (α, β, γ and p120) to facilitate metastasis. An increase in N-cadherin with down regulation of E-cadherin occurs during epithelial mesenchymal transition. Overexpression of N-cadherin is associated with cell cycle arrest, which correlates with a similar property of cancer stem cells (CSC). Connexin expression, which is important in CSC dormancy, is regulated by N-cadherin. This review discusses the potential of N-cadherin to be involved in maintaining CSCs, and to investigate pathways in N-cadherin expression. A better understanding of the role of N-Cadherin in CSC biology may identify new targets for the treatment of cancer.

scholarly journals HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markers

2018 ◽  
Author(s):  
Audrey T. Lin ◽  
Cindy G. Santander ◽  
Fabricia F. Nascimento ◽  
Emanuele Marchi ◽  
Timokratis Karamitros ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Human Genome ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Mesenchymal Transition

AbstractEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and rec’s correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.ImportanceIn this study, we find that human endogenous retrovirus HERV-K (HML-2)-encoded genes np9 and rec are correlated with the expression of many biomarkers associated with cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). There has been a significant effort to develop novel treatments targeting CSC and EMT-specific signalling pathways and cell surface markers. This research describes HERV-K (HML-2) as interacting or being part of the regulatory network that make up reversible cell state switching in EMT. Our findings suggest these specific HERVs may be good candidate biomarkers in identifying the transitional CSC-like states that are present during the progression of EMT and cancer metastasis.

scholarly journals Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4985
Author(s):  
Saima Usman ◽  
Naushin H. Waseem ◽  
Thuan Khanh Ngoc Nguyen ◽  
Sahar Mohsin ◽  
Ahmad Jamal ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cells ◽  
Type I ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Type Iii ◽  
Tumour Spread ◽  
Molecular Events

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.

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