Polymer-Coated Extracellular Vesicles for Selective Codelivery of Chemotherapeutics and siRNA to Cancer Cells

Extracellular Vesicles (EVs) secreted by cancer cells have a key role in the cancer microenvironment and progression. Previous studies have mainly focused on molecular functions, cellular components and biological processes...

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

Membranes ◽

10.3390/membranes11030199 ◽

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.

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Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

PROTEOMICS ◽

10.1002/pmic.202000098 ◽

2021 ◽

pp. 2000098

Author(s):

Annalisa L.E. Carli ◽

Shoukat Afshar‐Sterle ◽

Alin Rai ◽

Haoyun Fang ◽

Ryan O'Keefe ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Stem Cell Marker ◽

Cancer Stem Cell Marker ◽

Cell Marker ◽

Gastric Cancer Cells ◽

Migratory Phenotype

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Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro

Journal of Radiation Research ◽

10.1093/jrr/rrz001 ◽

2019 ◽

Vol 60 (3) ◽

pp. 289-297 ◽

Cited By ~ 17

Author(s):

Agata Abramowicz ◽

Anna Wojakowska ◽

Lukasz Marczak ◽

Malgorzata Lysek-Gladysinska ◽

Mateusz Smolarz ◽

...

Keyword(s):

Head And Neck Cancer ◽

Ionizing Radiation ◽

Head And Neck ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Neck Cancer

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Snail Overexpression Alters the microRNA Content of Extracellular Vesicles Released from HT29 Colorectal Cancer Cells and Activates Pro-Inflammatory State In Vivo

Cancers ◽

10.3390/cancers13020172 ◽

2021 ◽

Vol 13 (2) ◽

pp. 172

Author(s):

Izabela Papiewska-Pająk ◽

Patrycja Przygodzka ◽

Damian Krzyżanowski ◽

Kamila Soboska ◽

Izabela Szulc-Kiełbik ◽

...

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Colorectal Cancer Cells ◽

Microrna Profile ◽

Inflammatory State ◽

Metastatic Process

During metastasis, cancer cells undergo phenotype changes in the epithelial-mesenchymal transition (EMT) process. Extracellular vesicles (EVs) released by cancer cells are the mediators of intercellular communication and play a role in metastatic process. Knowledge of factors that influence the modifications of the pre-metastatic niche for the migrating carcinoma cells is important for prevention of metastasis. We focus here on how cancer progression is affected by EVs released from either epithelial-like HT29-cells or from cells that are in early EMT stage triggered by Snail transcription factor (HT29-Snail). We found that EVs released from HT29-Snail, as compared to HT29-pcDNA cells, have a different microRNA profile. We observed the presence of interstitial pneumonias in the lungs of mice injected with HT29-Snail cells and the percent of mice with lung inflammation was higher after injection of HT29-Snail-EVs. Incorporation of EVs released from HT29-pcDNA, but not released from HT29-Snail, leads to the increased secretion of IL-8 from macrophages. We conclude that Snail modifications of CRC cells towards more invasive phenotype also alter the microRNA cargo of released EVs. The content of cell-released EVs may serve as a biomarker that denotes the stage of CRC and EVs-specific microRNAs may be a target to prevent cancer progression.

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Stromal-derived extracellular vesicles suppress proliferation of bone metastatic cancer cells mediated by ERK2

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-20-0981 ◽

2021 ◽

pp. molcanres.MCR-20-0981-E.2020

Author(s):

Alison B. Shupp ◽

Manish Neupane ◽

Lebaron C Agostini ◽

Gang Ning ◽

Jonathan R. Brody ◽

...

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Metastatic Cancer ◽

Metastatic Cancer Cells

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TAMI-73. GLIOBLASTOMA CELL POPULATIONS WITH DISTINCT ONCOGENIC PROGRAMS RELEASE PODOPLANIN AS PROCOAGULANT EXTRACELLULAR VESICLES

Neuro-Oncology ◽

10.1093/neuonc/noab196.855 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi213-vi213

Author(s):

Nadim Tawil ◽

Rayhaan Bassawon ◽

Brian Meehan ◽

Laura Montermini ◽

Ali Nehme ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Extracellular Vesicles ◽

Glioblastoma Cell ◽

Activation Markers ◽

Increased Risk ◽

Gradient Fractionation ◽

D Dimer

Abstract BACKGROUND Vascular anomalies, including thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of dysregulated cancer cell genome and epigenome. Up-regulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk of venous thromboembolism in glioblastoma patients. Thus, regulation of this platelet activating protein by transforming events and release from cancer cells is of considerable interest. AIMS I. Investigate the pattern of PDPN expression and characterize PDPN-expressing cellular populations in GBM. II. Evaluate the contribution of oncogenic drivers to PDPN expression in GBM models. III. Investigate the potential involvement of extracellular vesicles (EVs) as a mechanism for systemic dissemination of PDPN and tissue factor (TF). IV. Examine the role of PDPN in intratumoral and systemic thrombosis. METHODS Bioinformatics (single-cell and bulk transcriptome data mining), GBM cell lines and stem cell lines, xenograft models in mice, ELISA assays for PDPN and TF, platelet (PF4) and clotting activation markers (D-dimer), EV electron microscopy, density gradient fractionation, and nano-flow cytometry. RESULTS PDPN is expressed by distinct glioblastoma cell subpopulations (mesenchymal) and downregulated by oncogenic mutations of EGFR and IDH1 genes, via changes in chromatin modifications (EZH2) and DNA methylation, respectively. GBM cells exteriorize PDPN and/or TF as cargo of exosome-like EVs shed both in vitro and in vivo. Injection of glioma PDPN-EVs activates platelets. Increase of platelet activation (PF4) or coagulation markers (D-dimer) occurs in mice harboring the corresponding glioma xenografts expressing PDPN or TF, respectively. Co-expression of PDPN and TF by GBM cells cooperatively increases tumor microthrombosis. CONCLUSION Distinct cellular subsets drive multiple facets of GBM-associated thrombosis and may represent targets for diagnosis and intervention. We suggest that the preponderance of PDPN expression as a risk factor in glioblastoma and the involvement of platelets may merit investigating anti-platelets for potential inclusion in thrombosis management in GBM.

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Extracellular vesicles produced in B cells deliver tumor suppressor miR-335 to breast cancer cells disrupting oncogenic programming in vitro and in vivo

Scientific Reports ◽

10.1038/s41598-018-35968-2 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Gonzalo Almanza ◽

Jeffrey J. Rodvold ◽

Brian Tsui ◽

Kristen Jepsen ◽

Hannah Carter ◽

...

Keyword(s):

Breast Cancer ◽

B Cells ◽

Tumor Suppressor ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Breast Cancer Cells

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TGFBR2‑dependent alterations of microRNA profiles in extracellular vesicles and parental colorectal cancer cells

International Journal of Oncology ◽

10.3892/ijo.2019.4859 ◽

2019 ◽

Cited By ~ 1

Author(s):

Fabia Fricke ◽

Veronika Mussack ◽

Dominik Buschmann ◽

Ingrid Hausser ◽

Michael Pfaffl ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Colorectal Cancer Cells

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

Pharmaceutics ◽

10.3390/pharmaceutics13111911 ◽

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.

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