scholarly journals Extracellular vesicles as biomarkers and therapeutic targets for cancer

2020 ◽  
Vol 318 (1) ◽  
pp. C29-C39 ◽  
Author(s):  
Fumihiko Urabe ◽  
Nobuyoshi Kosaka ◽  
Kagenori Ito ◽  
Takahiro Kimura ◽  
Shin Egawa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Therapeutic Targets ◽  
Membrane Vesicles ◽  
Clinical Applications ◽  
Research Knowledge ◽  
Cellular Processes ◽  
Novel Strategy ◽  
Almost All

Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, the unveiling of the precise mechanism of intercellular communication via EVs in cancer patients will provide a novel strategy for cancer treatment. Furthermore, a focus on the contents of EVs could promote the use of EVs in body fluids as clinically useful diagnostic and prognostic biomarkers. In this review, we summarize the current research knowledge on EVs as biomarkers and therapeutic targets and discuss their potential clinical applications.

scholarly journals Trastuzumab Modulates the Protein Cargo of Extracellular Vesicles Released by ERBB2+ Breast Cancer Cells

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 199
Author(s):  
Silvia Marconi ◽  
Sara Santamaria ◽  
Martina Bartolucci ◽  
Sara Stigliani ◽  
Cinzia Aiello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Culture Supernatant ◽  
High Resolution Mass Spectrometry ◽  
Recombinant Antibody ◽  
Target Cells ◽  
Cellular Processes ◽  
Erbb2 Signaling

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is an ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles (EVs) released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here, we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Trastuzumab (Tz) induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. Because these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

scholarly journals Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1911
Author(s):  
Anastasiya Oshchepkova ◽  
Oleg Markov ◽  
Evgeniy Evtushenko ◽  
Alexander Chernonosov ◽  
Elena Kiseleva ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Cytochalasin B ◽  
Drug Carrier ◽  
Membrane Vesicles ◽  
Nucleic Acid Delivery ◽  
Isolation And Purification ◽  
Cellular Origin ◽  
Efficient Uptake

The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due to their laborious isolation and purification procedures. Alternatively, mimetic vesicles prepared from the cellular plasma membrane can be used in the same way as natural EVs. For example, a cytoskeleton-destabilizing agent, such as cytochalasin B, allows the preparation of membrane vesicles by a series of centrifugations. Here, we prepared cytochalasin-B-inducible nanovesicles (CINVs) of various cellular origins and studied their tropism in different mammalian cells. We observed that CINVs derived from human endometrial mesenchymal stem cells exhibited an enhanced affinity to epithelial cancer cells compared to myeloid, lymphoid or neuroblastoma cancer cells. The dendritic cell-derived CINVs were taken up by all studied cell lines with a similar efficiency that differed from the behavior of DC-derived EVs. The ability of cancer cells to internalize CINVs was mainly determined by the properties of recipient cells, and the cellular origin of CINVs was less important. In addition, receptor-mediated interactions were shown to be necessary for the efficient uptake of CINVs. We found that CINVs, derived from late apoptotic/necrotic cells (aCINVs) are internalized by in myelogenous (K562) 10-fold more efficiently than CINVs, and interact much less efficiently with melanocytic (B16) or epithelial (KB-3-1) cancer cells. Finally, we found that CINVs caused a temporal and reversible drop of the rate of cell division, which restored to the level of control cells with a 24 h delay.

scholarly journals The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenglong Li
Keyword(s):  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Bone Sarcoma ◽  
Biologically Active ◽  
Signal Molecules ◽  
Diagnosis And Prognosis ◽  
Bone Sarcomas ◽  
Basic Characteristics ◽  
Almost All ◽  
Sarcoma Cells

AbstractBone sarcomas are rare cancers accompanied by metastatic disease, mainly including osteosarcoma, Ewing sarcoma and chondrosarcoma. Extracellular vesicles (EVs) are membrane vesicles released by cells in the extracellular matrix, which carry important signal molecules, can stably and widely present in various body fluids, such as plasma, saliva and scalp fluid, spinal cord, breast milk, and urine liquid. EVs can transport almost all types of biologically active molecules (DNA, mRNA, microRNA (miRNA), proteins, metabolites, and even pharmacological compounds). In this review, we summarized the basic biological characteristics of EVs and focused on their application in bone sarcomas. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. The role of EVs in bone sarcoma has been analyzed point-by-point. In the microenvironment of bone sarcoma, bone sarcoma cells, mesenchymal stem cells, immune cells, fibroblasts, osteoclasts, osteoblasts, and endothelial cells coexist and interact with each other. EVs play an important role in the communication between cells. Based on multiple functions in bone sarcoma, this review provides new ideas for the discovery of new therapeutic targets and new diagnostic analysis.

scholarly journals On the Choice of the Extracellular Vesicles for Therapeutic Purposes

2019 ◽  
Vol 20 (2) ◽  
pp. 236 ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Mariantonia Logozzi ◽  
Antonella Marino Gammazza ◽  
Davide Mizzoni ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Free Form ◽  
Target Cells ◽  
Disease Biomarkers ◽  
Cellular Source ◽  
Therapeutic Molecules

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of disease biomarkers and have high potential benefits in regenerative medicine. Indeed, they deliver both chemical and bio-molecules in a way that within exosomes drugs are more effective that in their exosome-free form. Thus, to date, we know that exosomes are shuttle disease biomarkers and probably the most effective way to deliver therapeutic molecules within target cells. However, we do not know exactly which exosomes may be used in therapy in avoiding side effects as well. In regenerative medicine, it will be ideal to use autologous exosomes, but it seems not ideal to use plasma-derived exosomes, as they may contain potentially dangerous molecules. Here, we want to present and discuss a contradictory relatively unmet issue that is the lack of a general agreement on the choice for the source of extracellular vesicles for therapeutic use.

scholarly journals Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglong Li ◽  
Wei Wang
Keyword(s):  
Bone Metastasis ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Bone Cells ◽  
Membrane Vesicles ◽  
Metastatic Tumor ◽  
Cell Types ◽  
Biological Phenomena ◽  
Breast And Prostate Cancer ◽  
Metastatic Sites

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15–20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transporting intracellular substances. Recent studies have implicated EVs in the development of cancer. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area. This review is focused on the role of tumor-derived EVs in bone metastasis and possible regulatory mechanisms.

scholarly journals Trastuzumab Modulates the Protein Cargo of Extracellular Vesicles Released by ERBB2+ Breast Cancer Cells

2021 ◽  
Author(s):  
Silvia Marconi ◽  
Sara Santamaria ◽  
Martina Bertolucci ◽  
Sara Stigliani ◽  
Cinzia Aiello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Culture Supernatant ◽  
High Resolution Mass Spectrometry ◽  
Recombinant Antibody ◽  
Target Cells ◽  
Cellular Processes ◽  
Erbb2 Signaling

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is a ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance, and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Tz induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. As these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

scholarly journals Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions and Applications

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Zhang ◽  
Ming Zhao ◽  
Qianjin Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Clinical Research ◽  
Extracellular Vesicles ◽  
Lupus Erythematosus ◽  
Membrane Vesicles ◽  
Systemic Lupus ◽  
Almost All ◽  
Extracellular Environment

In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.

Linoleic acid induces secretion of extracellular vesicles from MDA-MB-231 breast cancer cells that mediate cellular processes involved with angiogenesis in HUVECs

2021 ◽  
Vol 153 ◽  
pp. 106519
Author(s):  
Alejandra Garcia-Hernandez ◽  
Elizabeth Leal-Orta ◽  
Javier Ramirez-Ricardo ◽  
Pedro Cortes-Reynosa ◽  
Rocio Thompson-Bonilla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Linoleic Acid ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Cellular Processes

scholarly journals The Emerging World of Membrane Vesicles: Functional Relevance, Theranostic Avenues and Tools for Investigating Membrane Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Aswin T. Srivatsav ◽  
Shobhna Kapoor
Keyword(s):  
Lipid Membrane ◽  
Vaccine Development ◽  
Membrane Vesicles ◽  
Membrane Function ◽  
Functional Roles ◽  
Cellular Processes ◽  
Essential Components ◽  
Lipid Organization ◽  
Specific Proteins ◽  
Functional Relevance

Lipids are essential components of cell membranes and govern various membrane functions. Lipid organization within membrane plane dictates recruitment of specific proteins and lipids into distinct nanoclusters that initiate cellular signaling while modulating protein and lipid functions. In addition, one of the most versatile function of lipids is the formation of diverse lipid membrane vesicles for regulating various cellular processes including intracellular trafficking of molecular cargo. In this review, we focus on the various kinds of membrane vesicles in eukaryotes and bacteria, their biogenesis, and their multifaceted functional roles in cellular communication, host-pathogen interactions and biotechnological applications. We elaborate on how their distinct lipid composition of membrane vesicles compared to parent cells enables early and non-invasive diagnosis of cancer andtuberculosis, while inspiring vaccine development and drug delivery platforms. Finally, we discuss the use of membrane vesicles as excellent tools for investigating membrane lateral organization and protein sorting, which is otherwise challenging but extremely crucial for normal cellular functioning. We present current limitations in this field and how the same could be addressed to propel a fundamental and technology-oriented future for extracellular membrane vesicles.

On the Interplay of Extracellular Vesicles and Viral Infections

2020 ◽  
Vol 2 (1) ◽  
pp. 14-27
Author(s):  
Christoph Metzner ◽  
Marianne Zaruba
Keyword(s):  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Viral Infections ◽  
Membrane Vesicles ◽  
Enveloped Virus ◽  
Viral Particles ◽  
Potential Applications ◽  
Definition Of ◽  
Relationship Of ◽  
The Relationship

A broad definition of extracellular vesicles – lipid membrane enclosed vesicles of a given size range, produced by cells into the surrounding media and unable to replicate independently – does not only apply to exosomes or microvesicles produced by eukaryotic cells, outer membrane or outer-inner membrane vesicles produced by gram-negative bacteria and membrane vesicles produced by gram-positive bacteria (and archaea), but also extends to enveloped virus particles. They share biophysical and biochemical characteristics as well as functional properties, making it a challenge to distinguish between types of vesicles. In this review, we will briefly introduce different extracellular vesicles before concentrating on the relationship of viral particles to extracellular vesicles, taking practical issues into consideration as well as molecular interactions and the subsequent effects on infectivity and pathogenesis. Finally, we will briefly discuss potential applications of the relationship between extracellular vesicles and viral particles.

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