scholarly journals The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2435
Author(s):  
Thomas J. Brown ◽  
Victoria James
Keyword(s):  
Systematic Review ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Multiple Cancer ◽  
Therapeutic Targeting ◽  
Small Component ◽  
Facilitated Communication ◽  
Cell Microenvironment ◽  
Cancer Types

Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.

scholarly journals The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3949
Author(s):  
Federica Rascio ◽  
Federica Spadaccino ◽  
Maria Teresa Rocchetti ◽  
Giuseppe Castellano ◽  
Giovanni Stallone ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Akt Pathway ◽  
Invasion And Metastasis ◽  
Pathogenic Role ◽  
Multiple Cancer ◽  
Downstream Target ◽  
Cancer Types ◽  
Multi Level ◽  
Survival Mechanisms

The PI3K/AKT pathway is one of the most frequently over-activated intracellular pathways in several human cancers. This pathway, acting on different downstream target proteins, contributes to the carcinogenesis, proliferation, invasion, and metastasis of tumour cells. A multi-level impairment, involving mutation and genetic alteration, aberrant regulation of miRNAs sequences, and abnormal phosphorylation of cascade factors, has been found in multiple cancer types. The deregulation of this pathway counteracts common therapeutic strategies and contributes to multidrug resistance. In this review, we underline the involvement of this pathway in patho-physiological cell survival mechanisms, emphasizing its key role in the development of drug resistance. We also provide an overview of the potential inhibition strategies currently available.

scholarly journals The Expression of miRNAs in Human Ovaries, Oocytes, Extracellular Vesicles, and Early Embryos: A Systematic Review

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1564 ◽  
Author(s):  
Albert Salas-Huetos ◽  
Emma R. James ◽  
Kenneth I. Aston ◽  
Timothy G. Jenkins ◽  
Douglas T. Carrell ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Mirna Expression ◽  
Observational Studies ◽  
Reproductive Function ◽  
Human Reproduction ◽  
Reproductive Tissues ◽  
Early Embryos ◽  
Human Reproductive

The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.

scholarly journals TMIC-56. ROLE OF HUMAN BRAIN TUMOR STEM CELLS-DERIVED EXTRACELLULAR VESICLES ON THE PHENOTYPIC TRANSDIFFERENTIATION OF HUMAN NEURAL PROGENITOR CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi260-vi260
Author(s):  
Natanael Zarco ◽  
Emily Norton ◽  
Montserrat Lara-Velazquez ◽  
Anna Carrano ◽  
Alfredo Quinones-Hinojosa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Primary Cultures ◽  
Adult Brain ◽  
Cell Subpopulation ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

Abstract Glioblastoma (GBM) is the most aggressive of all the brain tumors with a median patient survival less than 15 months. Despite of surgical resection, radiotherapy, and chemotherapy, recurrence rate is almost 100%. A great percentage of GBM tumors (~60%) infiltrate and contact the ventricular-subventricular zone (V-SVZ). Interestingly, these tumors are the most aggressive, and invariably lead to higher distal recurrence rates, shorter time to tumor progression, and lower overall survival of the patient. The reason for this role of V-SVZ-proximity on the outcome of GBM patients is unknown. We suggest that a potential explanation is the interaction of GBM with the V-SVZ. This region is the largest neurogenic niche in the adult brain where neural stem cells (NSCs) give rise to newborn neuroblasts that migrate toward the olfactory bulb. In GBM there is a cell subpopulation called brain tumor stem cells (BTSCs) with NSCs-like characteristics, but with added potential for tumor initiation, recurrence and invasiveness. Tumor microenvironment plays an important role in migration and invasion process. In the present work, we used the total exosome isolation kit to purify Extracellular Vesicles (EVs) from human primary cultures of BTSCs. We determined that BTSCs-derived EVs contain specific information that is transfer to primary cultures of human Neural Progenitors Cells (NPCs) modulating their proliferation rate, cell viability, and migration. In addition, we identify that NPCs taken up BTSCs-derived EVs and significantly increase the expression levels of stemness-related genes such as Nestin, Nanog, and Sox2, suggesting that a phenotypic transdifferentiation is being carry out. These results support our hypothesis that GBM modulate the tumor microenvironment close to the V-SVZ by releasing EVs that target cellular components in this region and promote their phenotypic transformation, highlighting that NPCs biology changes in the context of tumor environment.

scholarly journals TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

2020 ◽  
Vol 49 (D1) ◽  
pp. D1420-D1430
Author(s):  
Dongqing Sun ◽  
Jin Wang ◽  
Ya Han ◽  
Xin Dong ◽  
Jun Ge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Large Scale ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Multiple Cancer ◽  
Web Resource ◽  
Cancer Types

Abstract Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors but posed computational challenges on integrating and utilizing the massive published datasets to inform immunotherapy. Here, we present Tumor Immune Single Cell Hub (TISCH, http://tisch.comp-genomics.org), a large-scale curated database that integrates single-cell transcriptomic profiles of nearly 2 million cells from 76 high-quality tumor datasets across 27 cancer types. All the data were uniformly processed with a standardized workflow, including quality control, batch effect removal, clustering, cell-type annotation, malignant cell classification, differential expression analysis and functional enrichment analysis. TISCH provides interactive gene expression visualization across multiple datasets at the single-cell level or cluster level, allowing systematic comparison between different cell-types, patients, tissue origins, treatment and response groups, and even different cancer-types. In summary, TISCH provides a user-friendly interface for systematically visualizing, searching and downloading gene expression atlas in the TME from multiple cancer types, enabling fast, flexible and comprehensive exploration of the TME.

scholarly journals Extracellular Vesicles: Evolving Factors in Stem Cell Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Muhammad Nawaz ◽  
Farah Fatima ◽  
Krishna C. Vallabhaneni ◽  
Patrice Penfornis ◽  
Hadi Valadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cell Biology ◽  
Trophic Factors ◽  
Stem Cell Biology ◽  
Cell Fates ◽  
Bidirectional Communication

Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

scholarly journals The Role of Extracellular Vesicles in Cancer: Cargo, Function, and Therapeutic Implications

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 93 ◽  
Author(s):  
James Jabalee ◽  
Rebecca Towle ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Tumor Stroma ◽  
Therapeutic Implications ◽  
Membrane Bound ◽  
Immune Destruction ◽  
And Function ◽  
Cargo Molecule

Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound structures that play key roles in intercellular communication. EVs are potent regulators of tumorigenesis and function largely via the shuttling of cargo molecules (RNA, DNA, protein, etc.) among cancer cells and the cells of the tumor stroma. EV-based crosstalk can promote proliferation, shape the tumor microenvironment, enhance metastasis, and allow tumor cells to evade immune destruction. In many cases these functions have been linked to the presence of specific cargo molecules. Herein we will review various types of EV cargo molecule and their functional impacts in the context of oncology.

scholarly journals Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiu-Li Ji ◽  
Xiao Liu ◽  
Jian-Ping Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Rna Modification ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Types ◽  
Pan Cancer

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

scholarly journals SALL4 and microRNA: The Role of Let-7

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1301
Author(s):  
Jun Liu ◽  
Madeline A. Sauer ◽  
Shaza Hussein ◽  
Junyu Yang ◽  
Daniel G. Tenen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Mammalian Development ◽  
Multiple Cancer ◽  
Self Renewal ◽  
Zinc Finger Transcription Factor ◽  
Different Types ◽  
Organ Specific ◽  
Cancer Types

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene fam-ily. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regard-ing how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as im-portant regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize cur-rent knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.

scholarly journals Molecular characterization and clinical relevance of m6A regulators across 33 cancer types

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Yongsheng Li ◽  
Jun Xiao ◽  
Jing Bai ◽  
Yi Tian ◽  
Yinwei Qu ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Critical Role ◽  
Genetic Alterations ◽  
Biological Processes ◽  
Valuable Resource ◽  
Multiple Cancer ◽  
Molecular Alterations ◽  
Prognostic Stratification ◽  
Cancer Types

Abstract The methylation of N6 adenosine (m6A) plays a critical role in diverse biological processes. However, knowledge regarding the reconstitution of m6A across cancer types is still lacking. Here, we systematically analyzed the molecular alterations and clinical relevance of m6A regulators across > 10,000 subjects representing 33 cancer types. We found that there are widespread genetic alterations to m6A regulators, and that their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Moreover, m6A regulators were found to be potentially useful for prognostic stratification, and we identified IGF2BP3 as a potential oncogene across multiple cancer types. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of m6A regulators in cancer.

scholarly journals Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 729 ◽  
Author(s):  
Pier Giorgio Amendola ◽  
Raphael Reuten ◽  
Janine Terra Erler
Keyword(s):  
Tumor Microenvironment ◽  
Structural Integrity ◽  
Lysyl Oxidase ◽  
Review Article ◽  
Amine Oxidases ◽  
Covalent Crosslinking ◽  
Cancer Types ◽  
Lox Inhibitors ◽  
Cell Phenotypes

Members of the lysyl oxidase (LOX) family are secreted copper-dependent amine oxidases that catalyze the covalent crosslinking of collagens and elastin in the extracellular matrix (ECM), an essential process for the structural integrity of all tissues. LOX enzymes can also remodel the tumor microenvironment and have been implicated in all stages of tumor initiation and progression of many cancer types. Changes in the ECM can influence several cancer cell phenotypes. Integrin adhesion complexes (IACs) physically connect cells with their microenvironment. This review article summarizes the main findings on the role of LOX proteins in modulating the tumor microenvironment, with a particular focus on how ECM changes are integrated by IACs to modulate cells behavior. Finally, we discuss how the development of selective LOX inhibitors may lead to novel and effective therapies in cancer treatment.

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