scholarly journals Role of Extracellular Vesicles in Hematological Malignancies

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Stefania Raimondo ◽  
Chiara Corrado ◽  
Lavinia Raimondi ◽  
Giacomo De Leo ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Hematological Malignancies ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Target Cells ◽  
Specific Cell ◽  
Cell Of Origin ◽  
Cell Functions

In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.

scholarly journals Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1495
Author(s):  
Egidia Costanzi ◽  
Rita Romani ◽  
Paolo Scarpelli ◽  
Ilaria Bellezza
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Target Cells ◽  
Prostate Cell ◽  
Prostate Cancer Therapy ◽  
Reverse Transcription Quantitative Pcr ◽  
Pc3 Cells

Prostate-derived extracellular vesicles (pEVs) may represent a way to selectively transport cargo molecules from the producing cells to the target cells to allow biological events, both in physiological and pathological circumstances. pEVs cargo participates in the modulation of the inflammatory responses in physiological conditions and during cancer progression. In the present study, we examined the expression levels of miRNA Let-7b, in both precursor and mature forms, in noncancerous and cancerous prostate cell lines, PNT2 and PC3 respectively, and in their extracellular vesicles (EVs) using reverse-transcription quantitative PCR strategies. We showed that miRNA Let-7b was highly expressed in noncancerous cells and strongly decreased in cancerous PC3 cells, while the opposite was observed in the respective EVs, thus supporting the tumor suppressor role of miRNA Let7-b. We also demonstrated that miRNA Let-7b can be transferred to THP-1 cells via EVs, which are known to induce TAM-like polarization. Our results support the view that miRNA Let-7 b, contained in PC3-derived EVs, is associated with the increase in the miRNA Let7-b observed in TAM-like macrophages. Overall, our results indicate that circulating EV-loaded miRNA might be useful biomarkers for prostate cancer progression and might also support a possible use of pEVs as targets for prostate cancer therapy.

scholarly journals Cancer associated-fibroblast-derived exosomes in cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Li ◽  
Adilson Fonseca Teixeira ◽  
Hong-Jian Zhu ◽  
Peter ten Dijke
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

scholarly journals Stem cells and extracellular vesicles: biological regulators of physiology and disease

2019 ◽  
Vol 317 (2) ◽  
pp. C155-C166 ◽  
Author(s):  
Theodor Borgovan ◽  
Lorin Crawford ◽  
Chibuikem Nwizu ◽  
Peter Quesenberry
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Malignant Phenotype ◽  
Marrow Mesenchymal Stem Cells ◽  
Physiological Homeostasis ◽  
Clinical Advances ◽  
Machine Learning Models

Many different subpopulations of subcellular extracellular vesicles (EVs) have been described. EVs are released from all cell types and have been shown to regulate normal physiological homeostasis, as well as pathological states by influencing cell proliferation, differentiation, organ homing, injury and recovery, as well as disease progression. In this review, we focus on the bidirectional actions of vesicles from normal and diseased cells on normal or leukemic target cells; and on the leukemic microenvironment as a whole. EVs from human bone marrow mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer, as well as mitigating radiation damage to marrow. The role of EVs in leukemia and their bimodal cross talk with the encompassing microenvironment remains to be fully characterized. This may provide insight for clinical advances via the application of EVs as potential therapy and the employment of statistical and machine learning models to capture the pleiotropic effects EVs endow to a dynamic microenvironment, possibly allowing for precise therapeutic intervention.

scholarly journals Extracellular Vesicles: A New Prospective in Crosstalk between Microenvironment and Stem Cells in Hematological Malignancies

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ilaria Laurenzana ◽  
Daniela Lamorte ◽  
Stefania Trino ◽  
Luciana De Luca ◽  
Concetta Ambrosino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Hematological Malignancies ◽  
Cell Communication ◽  
Target Cells ◽  
Neoplastic Cells ◽  
Hematopoietic Stem ◽  
Bm Niche ◽  
Bidirectional Interactions

The bone marrow (BM) microenvironment in hematological malignancies (HMs) comprises heterogeneous populations of neoplastic and nonneoplastic cells. Cancer stem cells (CSCs), neoplastic cells, hematopoietic stem cells (HSCs), and mesenchymal stromal/stem cells (MSCs) are all components of this microenvironment. CSCs are the HM initiators and are associated with neoplastic growth and drug resistance, while HSCs are able to reconstitute the entire hematopoietic system; finally, MSCs actively support hematopoiesis. In some HMs, CSCs and neoplastic cells compromise the normal development of HSCs and perturb BM-MSCs. In response, “reprogrammed” MSCs generate a favorable environment to support neoplastic cells. Extracellular vesicles (EVs) are an important cell-to-cell communication type in physiological and pathological conditions. In particular, in HMs, EV secretion participates to unidirectional and bidirectional interactions between neoplastic cells and BM cells. The transfer of EV molecular cargo triggers different responses in target cells; in particular, malignant EVs modify the BM environment in favor of neoplastic cells at the expense of normal HSCs, by interfering with antineoplastic immunity and participating in resistance to treatment. Here, we review the role of EVs in BM cell communication in physiological conditions and in HMs, focusing on the effects of BM niche EVs on HSCs and MSCs.

scholarly journals Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

2021 ◽  
Vol 22 (6) ◽  
pp. 2870
Author(s):  
Tsung-Chieh Lin ◽  
Michael Hsiao
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Prognostic Significance ◽  
Cell Types ◽  
Receptor Expression ◽  
Specific Cell ◽  
Signaling Axis

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

scholarly journals Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2963
Author(s):  
Grace Y. Sun ◽  
Xue Geng ◽  
Tao Teng ◽  
Bo Yang ◽  
Michael K. Appenteng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Localization ◽  
Cell Types ◽  
Molecular Structures ◽  
Specific Cell ◽  
Phospholipases A2 ◽  
Cell Functions ◽  
The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

scholarly journals Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

2019 ◽  
Vol 20 (22) ◽  
pp. 5527 ◽  
Author(s):  
Tünde Szatmári ◽  
Rita Hargitai ◽  
Géza Sáfrány ◽  
Katalin Lumniczky
Keyword(s):  
Ionizing Radiation ◽  
Extracellular Vesicles ◽  
Radiation Effects ◽  
Cell Types ◽  
Tumor Formation ◽  
The Body ◽  
Target Cells ◽  
Cell Of Origin ◽  
Radiation Induced ◽  
Almost All

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.

scholarly journals Role of the Exosome in Ovarian Cancer Progression and Its Potential as a Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1147 ◽  
Author(s):  
Koji Nakamura ◽  
Kenjiro Sawada ◽  
Masaki Kobayashi ◽  
Mayuko Miyamoto ◽  
Aasa Shimizu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Peritoneal Dissemination ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Target Cells ◽  
Distinct Form ◽  
Cargo Delivery ◽  
Different Cell Types

Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30–150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and lipids. Furthermore, therapeutic applications of exosomes as drug cargo delivery are attracting research interest because exosomes are stabilized in circulation. This review highlights the functions of exosomes in each process of the peritoneal dissemination of ovarian cancer and discusses their potential for cancer therapeutics.

scholarly journals Extracellular Vesicles and Their Role in the Spatial and Temporal Expansion of Tumor–Immune Interactions

2021 ◽  
Vol 22 (7) ◽  
pp. 3374
Author(s):  
Simone Lipinski ◽  
Katharina Tiemann
Keyword(s):  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cross Talk ◽  
Antitumor Immunity ◽  
Parental Cell ◽  
Cancer Diagnostics ◽  
Target Cells ◽  
Potential Use

Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. In cancer, the content of EVs derived from tumor cells is altered and can induce oncogenic reprogramming of target cells. As a result, tumor-derived EVs compromise antitumor immunity and promote cancer progression and spreading. However, this pro-oncogenic phenotype is constantly being challenged by EVs derived from the local tumor microenvironment and from remote sources. Here, we summarize the role of EVs in the tumor–immune cross-talk that includes, but is not limited to, immune cells in the tumor microenvironment. We discuss the potential of remotely released EVs from the microbiome and during physical activity to shape the tumor–immune cross-talk, directly or indirectly, and confer antitumor activity. We further discuss the role of proinflammatory EVs in the temporal development of the tumor–immune interactions and their potential use for cancer diagnostics.

scholarly journals The mini player with diverse functions: extracellular vesicles in cell biology, disease, and therapeutics

2021 ◽  
Author(s):  
Abhimanyu Thakur ◽  
Xiaoshan Ke ◽  
Ya-Wen Chen ◽  
Pedram Motallebnejad ◽  
Kui Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Biology ◽  
Cancer Biology ◽  
Cell Types ◽  
Research Progress ◽  
Drug Delivery Vehicles ◽  
Significant Research

AbstractExtracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.

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