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breast cancer exosomes

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https://www.readbyqxmd.com/read/27917441/size-selective-harvesting-of-extracellular-vesicles-for-strategic-analyses-towards-tumor-diagnoses
#1
Chihiro Manri, Takahide Yokoi, Hirokazu Nishida
Extracellular vesicles (EV), typified by exosomes or microvesicles, are expected to be effective diagnostic markers for cancers. The sizes of the vesicles range from 20 to 1000 nm, but the size-dependent variations of the contents of EVs are still poorly understood. We succeeded in the size-selective harvesting of the vesicles by utilizing the molecular weight-dependent characteristics of a variety of polyethylene glycols (PEG) as precipitating reagents and analyzed the antigens displayed on the surfaces of the vesicles and the miRNAs included in the vesicles from each size group...
December 5, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27906043/exosomes-play-an-important-role-in-the-process-of-psoralen-reverse-multidrug-resistance-of-breast-cancer
#2
Xiaohong Wang, Chengfeng Xu, Yitong Hua, Leitao Sun, Kai Cheng, Zhongming Jia, Yong Han, Jianli Dong, Yuzhen Cui, Zhenlin Yang
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo)...
December 1, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27897190/versatile-sensitive-liquid-chromatography-mass-spectrometry-implementation-of-10%C3%A2-%C3%AE-m-ot-columns-suitable-for-small-molecules-peptides-and-proteins
#3
T Vehus, H Roberg-Larsen, J Waaler, S Aslaksen, S Krauss, S R Wilson, E Lundanes
We have designed a versatile and sensitive liquid chromatographic (LC) system, featuring a monolithic trap column and a very narrow (10 μm ID) fused silica open tubular liquid chromatography (OTLC) separation column functionalized with C18-groups, for separating a wide range of molecules (from small metabolites to intact proteins). Compared to today's capillary/nanoLC approaches, our system provides significantly enhanced sensitivity (up to several orders) with matching or improved separation efficiency, and highly repeatable chromatographic performance...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#4
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27845903/myoferlin-is-a-novel-exosomal-protein-and-functional-regulator-of-cancer-derived-exosomes
#5
Arnaud Blomme, Karim Fahmy, Olivier Peulen, Brunella Costanza, Marie Fontaine, Ingrid Struman, Dominique Baiwir, Edwin de Pauw, Marc Thiry, Akeila Bellahcène, Vincent Castronovo, Andrei Turtoi
Exosomes are communication mediators participating in the intercellular exchange of proteins, metabolites and nucleic acids. Recent studies have demonstrated that exosomes are characterized by a unique proteomic composition that is distinct from the cellular one. The mechanisms responsible for determining the proteome content of the exosomes remain however obscure. In the current study we employ ultrastructural approach to validate a novel exosomal protein myoferlin. This is a multiple C2-domain containing protein, known for its conserved physiological function in endocytosis and vesicle fusion biology...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832183/tumor-cell-derived-exosomes-from-the-prostate-cancer-cell-line-tramp-c1-impair-osteoclast-formation-and-differentiation
#6
Terese Karlsson, Marie Lundholm, Anders Widmark, Emma Persson
Skeletal metastatic disease is a deleterious consequence of dissemination of tumor cells from numerous primary sites, such as prostate, lung and breast. Skeletal metastases are still incurable, resulting in development of clinical complications and decreased survival for cancer patients with metastatic disease. During the last decade, tumor cell-derived microvesicles have been identified and suggested to be involved in cancer disease progression. Whether cancer exosomes are involved in tumor and bone cell interactions in the metastatic site is still, however, a rather unexplored field...
2016: PloS One
https://www.readbyqxmd.com/read/27831634/exosomes-mediated-transfer-of-lncrna-uca1-results-in-increased-tamoxifen-resistance-in-breast-cancer-cells
#7
C-G Xu, M-F Yang, Y-Q Ren, C-H Wu, L-Q Wang
OBJECTIVE: In this study, we firstly compared the loading of urothelial carcinoma-associated 1 (UCA1) in exosomes between tamoxifen sensitive and tamoxifen resistant breast cancer cells and further investigated the role of exosomal transfer of UCA1 in the development of tamoxifen resistance in estrogen receptor (ER) positive breast cancer cells. MATERIALS AND METHODS: Exosomes were isolated from the culture medium of tamoxifen sensitive MCF-7 cells and tamoxifen resistant LCC2 cells...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27822407/exosomes-mediate-micrornas-transfer-in-breast-cancer-chemoresistance-regulation
#8
REVIEW
Juliana Carvalho Santos, Marcelo Lima Ribeiro, Luis Otávio Sarian, Manoela Marques Ortega, Sophie Françoise Derchain
Breast cancer is the most common and fatal type of cancer in women worldwide due to the metastatic process and resistance to treatment. Despite advances in molecular knowledge, little is known regarding resistance to chemotherapy. One highlighted aspect is the DNA damage response (DDR) pathway that is activated upon genotoxic damage, controlling the cell cycle arrest or DNA repair activation. Recently, studies have showed that cancer stem cells (CSCs) could promote chemoresistance through DDR pathway. Furthermore, it is known that the epithelial-mesenchymal transition (EMT) can generate cells with CSCs characteristics and therefore regulate the chemoresistance process...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27819324/a-rapid-automated-surface-protein-profiling-of-single-circulating-exosomes-in-human-blood
#9
Golam Kibria, Erika K Ramos, Katelyn E Lee, Sarah Bedoyan, Simo Huang, Ravand Samaeekia, Jaffre J Athman, Clifford V Harding, Jan Lötvall, Lyndsay Harris, Cheryl L Thompson, Huiping Liu
Circulating exosomes provide a promising approach to assess novel and dynamic biomarkers in human disease, due to their stability, accessibility and representation of molecules from source cells. However, this potential has been stymied by lack of approaches for molecular profiling of individual exosomes, which have a diameter of 30-150 nm. Here we report a rapid analysis approach to evaluate heterogeneous surface protein expression in single circulating exosomes from human blood. Our studies show a differential CD47 expression in blood-derived individual circulating exosomes that is correlated with breast cancer status, demonstrating a great potential of individual exosome profiles in biomarker discovery...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27800035/oncogene-knockdown-via-active-loading-of-small-rnas-into-extracellular-vesicles-by-sonication
#10
Tek N Lamichhane, Anjana Jeyaram, Divya B Patel, Babita Parajuli, Natalie K Livingston, Navein Arumugasaamy, John S Schardt, Steven M Jay
Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising drug delivery vehicles for small RNAs (siRNA and miRNA) due to their natural role in intercellular RNA transport. However, the application of EVs for therapeutic RNA delivery may be limited by loading approaches that can induce cargo aggregation or degradation. Here, we report the use of sonication as a means to actively load functional small RNAs into EVs. Conditions under which EVs could be loaded with small RNAs with minimal detectable aggregation were identified, and EVs loaded with therapeutic siRNA via sonication were observed to be taken up by recipient cells and capable of target mRNA knockdown leading to reduced protein expression...
September 2016: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/27760843/exosomal-annexin-a2-promotes-angiogenesis-and-breast-cancer-metastasis
#11
Sayantan Maji, Pankaj Chaudhary, Irina Akopova, Phung M Nguyen, Richard J Hare, Ignacy Gryczynski, Jamboor K Vishwanatha
: Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin A2 as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal-AnnexinA2 (exo-AnxA2) are still lacking. In this study, mechanistic insight was sought regarding exo-AnxA2 and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-AnxA2 in angiogenesis...
October 19, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27760789/the-biodistribution-and-immune-suppressive-effects-of-breast-cancer-derived-exosomes
#12
Shu Wen Wen, Jaclyn Sceneay, Luize Goncalves Lima, Christina S F Wong, Melanie Becker, Sophie Krumeich, Richard J Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S Parker, Andreas Möller
Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45(+) bone marrow-derived cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27693459/breast-cancer-secreted-mir-939-downregulates-ve-cadherin-and-destroys-the-barrier-function-of-endothelial-monolayers
#13
Martina Di Modica, Viola Regondi, Marco Sandri, Marilena V Iorio, Adriana Zanetti, Elda Tagliabue, Patrizia Casalini, Tiziana Triulzi
Exosomes-secreted microRNAs play an important role in metastatic spread. During this process breast cancer cells acquire the ability to transmigrate through blood vessels by inducing changes in the endothelial barrier. We focused on miR-939 that is predicted to target VE-cadherin, a component of adherens junction involved in vessel permeability. By in silico analysis miR-939 was found highly expressed in the basal-like tumor subtypes and in our cohort of 63 triple-negative breast cancers (TNBCs) its expression significantly interacted with lymph node status in predicting disease-free survival probability...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27617891/imaging-and-intracellular-tracking-of-cancer-derived-exosomes-using-single-molecule-localization-based-super-resolution-microscope
#14
Chen Chen, Shenfei Zong, Zhuyuan Wang, Ju Lu, Dan Zhu, Yizhi Zhang, Yiping Cui
Exosomes are small membrane vesicles secreted by cells and enriched with plenty of proteins. Considering their significant roles in different physical activities and potential value for diagnostic drug delivery, researchers have put great efforts in in vitro tracking and content analysis of exosomes. Recently, the emergence of different kinds of super-resolution microscopy provides powerful tools for exosome study. Here, we demonstrate the application of single-molecule localization based super-resolution imaging technique in the imaging and tracking of cancer-derived exosomes...
October 5, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27608715/plasma-exosome-micrornas-are-indicative-of-breast-cancer
#15
Bethany N Hannafon, Yvonne D Trigoso, Cameron L Calloway, Y Daniel Zhao, David H Lum, Alana L Welm, Zhizhuang J Zhao, Kenneth E Blick, William C Dooley, W Q Ding
BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin...
2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27589561/periostin-is-identified-as-a-putative-metastatic-marker-in-breast-cancer-derived-exosomes
#16
Ioulia Vardaki, Sophia Ceder, Dorothea Rutishauser, George Baltatzis, Theodoros Foukakis, Theocharis Panaretakis
Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines...
August 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27571936/circulating-intestine-derived-exosomal-mir-328-in-plasma-a-possible-biomarker-for-estimating-bcrp-function-in-the-human-intestines
#17
Keisuke Gotanda, Takeshi Hirota, Jumpei Saito, Masato Fukae, Yu Egashira, Noritomo Izumi, Mariko Deguchi, Miyuki Kimura, Shunji Matsuki, Shin Irie, Ichiro Ieiri
A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27569215/mesenchymal-stem-cell-derived-exosomes-stimulate-cycling-quiescence-and-early-breast-cancer-dormancy-in-bone-marrow
#18
Sarah A Bliss, Garima Sinha, Oleta A Sandiford, Lisa M Williams, Daniel J Engelberth, Khadidiatou Guiro, Leidy L Isenalumhe, Steven J Greco, Seda Ayer, Margarette Bryan, Rakesh Kumar, Nicholas M Ponzio, Pranela Rameshwar
Dormant breast cancers resurge as metastatic disease after a long dormancy period in the bone marrow, where cancer cells interact with mesenchymal stem cells (MSC). However, the nature of early interactions between breast cancer cells and MSCs in the bone marrow microenvironment that facilitate adaptation to a quiescent state remains poorly understood. Here, we report that breast cancer cells prime MSC to release exosomes containing distinct miRNA contents, such as miR-222/223, which in turn promotes quiescence in a subset of cancer cells and confers drug resistance...
October 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27566577/secretome-proteomics-reveals-candidate-non-invasive-biomarkers-of-brca1-deficiency-in-breast-cancer
#19
Marc Warmoes, Siu W Lam, Petra van der Groep, Janneke E Jaspers, Yvonne H C M Smolders, Leon de Boer, Thang V Pham, Sander R Piersma, Sven Rottenberg, Epie Boven, Jos Jonkers, Paul J van Diest, Connie R Jimenez
Breast cancer arising in female BRCA1 mutation carriers is characterized by an aggressive phenotype and early age of onset. We performed tandem mass spectrometry-based proteomics of secretomes and exosome-like extracellular vesicles from BRCA1-deficient and BRCA1-proficient murine breast tumor models to identify extracellular protein biomarkers, which can be used as an adjunct to current diagnostic modalities in patients with BRCA1-deficient breast cancer. We identified 2,107 proteins, of which 215 were highly enriched in the BRCA1-deficient secretome...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27558906/exosomes-increase-the-therapeutic-index-of-doxorubicin-in-breast-and-ovarian-cancer-mouse-models
#20
Mohamad Hadla, Stefano Palazzolo, Giuseppe Corona, Isabella Caligiuri, Vincenzo Canzonieri, Giuseppe Toffoli, Flavio Rizzolio
AIM: To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX). MATERIALS & METHODS: Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS. RESULTS: Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells...
September 2016: Nanomedicine
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