ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From 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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Polymer-Coated Extracellular Vesicles for Selective Codelivery of Chemotherapeutics and siRNA to Cancer Cells

ACS Applied Bio Materials ◽

10.1021/acsabm.0c01153 ◽

2021 ◽

Vol 4 (2) ◽

pp. 1294-1306

Author(s):

Yong-Yu Jhan ◽

Guillermo Palou Zuniga ◽

Kanwar Abhay Singh ◽

Akhilesh K. Gaharwar ◽

Daniel L. Alge ◽

...

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles

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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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The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Cancers ◽

10.3390/cancers13123040 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3040

Author(s):

Zainab Hussain ◽

Jeremy Nigri ◽

Richard Tomasini

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Extracellular Vesicles ◽

Cell Communication ◽

Pancreatic Tumors ◽

Mediated Communication ◽

Biological Impact ◽

Physiological Relevance ◽

Cellular Components ◽

Tumoral Cells

Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients’ care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells’ proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell–cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.

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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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