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Tumor-derived exosomes

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https://www.readbyqxmd.com/read/28090647/the-multifaceted-role-of-extracellular-vesicles-in-metastasis-priming-the-soil-for-seeding
#1
REVIEW
Brunna Dos Anjos Pultz, Felipe Andrés Cordero da Luz, Sara Socorro Faria, Leandro Peixoto Ferreira de Souza, Paula Cristina Brígido Tavares, Vivian Alonso Goulart, Wagner Fontes, Luiz Ricardo Goulart, Marcelo José Barbosa Silva
Extracellular vesicles (EVs), including exosomes, play a key role in inter and intracellular communication, promoting the proliferation and invasion of recipient cells to support tumor growth and metastasis. Metastasis comprises multiple steps that first include the detachment of tumor cells through epithelial to mesenchymal transition (EMT), allowing the physical dissemination to distant organs. Thereafter, cancer-derived exosomes are still critical components for preparing the tumor microenvironment by (i) enabling tumor cells to escape from the immunological surveillance and (ii) arranging the pre-metastatic site for the engraftment of detached cancer cells...
January 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#2
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28076321/secretion-modification-region-derived-peptide-blocks-exosome-release-and-mediates-cell-cycle-arrest-in-breast-cancer-cells
#3
Ming-Bo Huang, Ruben R Gonzalez, James Lillard, Vincent C Bond
PURPOSE: Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069806/dna-containing-exosomes-derived-from-cancer-cells-treated-with-topotecan-activate-a-sting-dependent-pathway-and-reinforce-antitumor-immunity
#4
Yuichi Kitai, Takumi Kawasaki, Takuya Sueyoshi, Kouji Kobiyama, Ken J Ishii, Jian Zou, Shizuo Akira, Tadashi Matsuda, Taro Kawai
Danger-associated molecular patterns derived from damaged or dying cells elicit inflammation and potentiate antitumor immune responses. In this article, we show that treatment of breast cancer cells with the antitumor agent topotecan (TPT), an inhibitor of topoisomerase I, induces danger-associated molecular pattern secretion that triggers dendritic cell (DC) activation and cytokine production. TPT administration inhibits tumor growth in tumor-bearing mice, which is accompanied by infiltration of activated DCs and CD8(+) T cells...
January 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28068409/reprogramming-malignant-cancer-cells-toward-a-benign-phenotype-following-exposure-to-human-embryonic-stem-cell-microenvironment
#5
Shufeng Zhou, Mohamed Abdouh, Vincenzo Arena, Manuel Arena, Goffredo Orazio Arena
The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28064454/hgf-met-in-cancer-progression-and-biomarker-discovery
#6
REVIEW
Kunio Matsumoto, Masataka Umitsu, Dinuka M De Silva, Arpita Roy, Donald P Bottaro
Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3-D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases respectively for invasion-metastasis and resistance against targeted drugs in cancers. Recent studies indicated that MET in tumor-derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification-induced MET activation and ligand-dependent MET activation in autocrine/paracrine manner are causes for resistance to EGF receptor tyrosine kinase inhibitors and ALK inhibitors...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28060758/exosomes-as-mediators-of-platinum-resistance-in-ovarian-cancer
#7
Jennifer Crow, Safinur Atay, Samagya Banskota, Brittany Artale, Sarah Schmitt, Andrew K Godwin
Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28009978/the-secretion-and-biological-function-of-tumor-suppressor-maspin-as-an-exosome-cargo-protein
#8
Ivory Dean, Sijana H Dzinic, M Margarida Bernardo, Yi Zou, Vickie Kimler, Xiaohua Li, Alexander Kaplun, James Granneman, Guangzhao Mao, Shijie Sheng
Maspin is an epithelial-specific tumor suppressor shown to exert its biological effects as an intracellular, cell membrane-associated, and secreted free molecule. A recent study suggests that upon DNA-damaging g-irradiation, tumor cells can secrete maspin as an exosome-associated protein. To date, the biological significance of exosomal secretion of maspin is unknown. The current study aims at addressing whether maspin is spontaneously secreted as an exosomal protein to regulate tumor/stromal interactions. We prepared exosomes along with cell extracts and vesicle-depleted conditioned media (VDCM) from normal epithelial (CRL2221, MCF-10A and BEAS-2B) and cancer (LNCaP, PC3 and SUM149) cell lines...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27965168/a-specific-spectral-signature-of-serum-and-plasma-derived-extracellular-vesicles-for-cancer-screening
#9
Christoph Krafft, Konrad Wilhelm, Anna Eremin, Sigrun Nestel, Nikolas von Bubnoff, Wolfgang Schultze-Seemann, Juergen Popp, Irina Nazarenko
In cancer, extracellular vesicles (EVs) contribute to tumor progression by regulating local and systemic effects. Being released into body fluids, EV may be used in nanomedicine as a valuable source for diagnostic biomarkers. In this work, infrared and Raman spectroscopy were used for comprehensive comparative analysis of cancer versus non-cancer EV and patient screening. Two different EV fractions enriched in exosomes and microvesicles were isolated by differential centrifugation from serum and plasma of cancer and non-cancer patients and from serum and plasma of a healthy donor...
December 10, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27956246/global-profiling-of-viral-and-cellular-non-coding-rnas-in-epstein-barr-virus-induced-lymphoblastoid-cell-lines-and-released-exosome-cargos
#10
Alessia Gallo, Serena Vella, Monica Miele, Francesca Timoneri, Mariangela Di Bella, Silvia Bosi, Marco Sciveres, Pier Giulio Conaldi
The human EBV-transformed lymphoblastoid cell line (LCL), obtained by infecting peripheral blood monocular cells with Epstein-Barr Virus, has been extensively used for human genetic, pharmacogenomic, and immunologic studies. Recently, the role of exosomes has also been indicated as crucial in the crosstalk between EBV and the host microenvironment. Because the role that the LCL and LCL exosomal cargo might play in maintaining persistent infection, and since little is known regarding the non-coding RNAs of LCL, the aim of our work was the comprehensive characterization of this class of RNA, cellular and viral miRNAs, and cellular lncRNAs, in LCL compared with PBMC derived from the same donors...
December 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27956165/cancer-derived-exosomic-micrornas-shape-the-immune-system-within-the-tumor-microenvironment-state-of-the-art
#11
REVIEW
Francesca Fanini, Muller Fabbri
In recent years there has been an increasing interest of the scientific community on exosome research, with particular emphasis on the mechanisms by which tumor-derived exosomes can promote tumor growth. Particularly, exosome-mediated immune-escape is under deep investigation and still represents a quite controversial issue. Tumor-derived exosomes are carriers of information able to reprogram functions of immune target cells, influencing their development, maturation, and antitumor activities. They deliver proteins similar to those of the parent cancer cells, but also genetic messages like genomic DNA, mRNA, and microRNAs (miRNAs) that ultimately share the so called "tumor microenvironment" in a pro-tumoral fashion...
December 9, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27941674/biology-therapy-and-implications-of-tumor-exosomes-in-the-progression-of-melanoma
#12
REVIEW
Allison L Isola, Kevinn Eddy, Suzie Chen
Cancer is the second leading cause of death in the United States, and about 6% of the estimated cancer diagnoses this year will be melanoma cases. Melanomas are derived from transformation of the pigment producing cells of the skin, melanocytes. Early stage melanoma is usually curable by surgical resection, but late stage or subsequent secondary metastatic tumors are treated with some success with chemotherapies, radiation and/or immunotherapies. Most cancer patients die from metastatic disease, which is especially the case in melanoma...
December 9, 2016: Cancers
https://www.readbyqxmd.com/read/27930879/melanoma-exosomes-deliver-a-complex-biological-payload-that-upregulates-ptpn11-to-suppress-t-lymphocyte-function
#13
Yueting Wu, Wentao Deng, Emily Chambers McGinley, David J Klinke
As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27913196/nf-kb-regulated-exosomal-mir-155-promotes-the-inflammation-associated-with-arsenite-carcinogenesis
#14
Chao Chen, Fei Luo, Xinlu Liu, Lu Lu, Hui Xu, Qianlei Yang, Junchao Xue, Le Shi, Jun Li, Aihua Zhang, Qizhan Liu
In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27909058/secreted-glioblastoma-nanovesicles-contain-intracellular-signaling-proteins-and-active-ras-incorporated-in-a-farnesylation-dependent-manner
#15
Natalie Luhtala, Aaron Aslanian, John R Yates, Tony Hunter
Glioblastomas (GBMs) are malignant brain tumors with a median survival of less than 18 months. Redundancy of signaling pathways represented within GBMs contributes to their therapeutic resistance. Exosomes are extracellular nanovesicles released from cells and present in human biofluids that represent a possible biomarker of tumor signaling state that could aid in personalized treatment. Herein, we demonstrate that mouse GBM cell-derived extracellular nanovesicles resembling exosomes from an H-RasV12 myr-Akt mouse model for GBM are enriched for intracellular signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and contain active Ras...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902458/dna-sequences-within-glioma-derived-extracellular-vesicles-can-cross-the-intact-blood-brain-barrier-and-be-detected-in-peripheral-blood-of-patients
#16
Noemí García-Romero, Josefa Carrión-Navarro, Susana Esteban-Rubio, Elisa Lázaro-Ibáñez, María Peris-Celda, Marta M Alonso, Juan Guzmán-De-Villoria, Carlos Fernández-Carballal, Ana Ortiz de Mendivil, Sara García-Duque, Carmen Escobedo-Lucea, Ricardo Prat-Acín, Cristóbal Belda-Iniesta, Angel Ayuso-Sacido
Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs-apoptotic bodies, shedding microvesicles and exosomes-cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894084/curcumin-increases-exosomal-tcf21-thus-suppressing-exosome-induced-lung-cancer
#17
Hao Wu, Jingcheng Zhou, Chao Zeng, Da Wu, Zhimin Mu, Baokun Chen, Yuancai Xie, Yiwang Ye, Jixian Liu
Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888803/exosomal-long-noncoding-rna-crnde-h-as-a-novel-serum-based-biomarker-for-diagnosis-and-prognosis-of-colorectal-cancer
#18
Tong Liu, Xin Zhang, Shanyu Gao, Fangmiao Jing, Yongmei Yang, Lutao Du, Guixi Zheng, Peilong Li, Chen Li, Chuanxin Wang
Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27882696/fetuin-a-alpha-2hs-glycoprotein-modulates-growth-motility-invasion-and-senescence-in-high-grade-astrocytomas
#19
Gladys N Nangami, Amos M Sakwe, Michael G Izban, Tanu Rana, Philip E Lammers, Portia Thomas, Zhenbang Chen, Josiah Ochieng
Glioblastomas (high-grade astrocytomas) are highly aggressive brain tumors with poor prognosis and limited treatment options. In the present studies, we have defined the role of fetuin-A, a liver-derived multifunctional serum protein, in the growth of an established glioblastoma cell line, LN229. We hereby demonstrate that these cells synthesize ectopic fetuin-A which supports their growth in culture in the absence of serum. We have demonstrated that a panel of tissue microarray (TMA) of glioblastomas also express ectopic fetuin-A...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27882487/delivery-of-small-interfering-rna-to-inhibit-vascular-endothelial-growth-factor-in-zebrafish-using-natural-brain-endothelia-cell-secreted-exosome-nanovesicles-for-the-treatment-of-brain-cancer
#20
Tianzhi Yang, Brittany Fogarty, Bret LaForge, Salma Aziz, Thuy Pham, Leanne Lai, Shuhua Bai
Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0...
November 23, 2016: AAPS Journal
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