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Tumor-derived exosomes

Susana Junqueira-Neto, Inês A Batista, José Luís Costa, Sónia A Melo
Liquid biopsy represents the analysis of tumor-derived material in the blood and other body fluids of cancer patients. This portrays a minimally invasive detection tool for molecular biomarkers. Liquid biopsy has emerged as a complementary or alternative method to surgical biopsy. This non-invasive detection tool overcomes the recurrent problems in the clinical assessment of tumors that stem from the lack of accessibility to the tumor tissue and its clonal heterogeneity. Moreover, body fluid-derived components have shown to reflect the genetic profile of both primary and metastatic lesions and provide a real-time monitoring of tumor dynamics, representing a great promise for personalized medicine...
February 15, 2019: Acta Cytologica
Catarina Roma-Rodrigues, Rita Mendes, Pedro V Baptista, Alexandra R Fernandes
Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e...
February 15, 2019: International Journal of Molecular Sciences
Federico Cocozza, Florencia Menay, Rodrigo Tsacalian, Analía Elisei, Pura Sampedro, Ivana Soria, Claudia Waldner, María José Gravisaco, Claudia Mongini
Exosomes are 60-150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield...
February 15, 2019: Vaccine
Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish K Agrawal, Al-Hassan Kyakulaga, Sarah A Wilcher, Ramesh C Gupta
Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5'-32 P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable...
February 13, 2019: Cancer Letters
Zhanjun Ma, Xue Cui, Li Lu, Guohu Chen, Yang Yang, Yan Hu, Yubao Lu, Zhangqi Cao, Yan Wang, Xuexi Wang
BACKGROUND: Exosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have been used as tumor-tropic vectors for tumor therapy; however, the safety of such therapeutic use of MSCs is unknown. In this study, we investigated the role of glioma cell-derived exosomes in the tumor-like phenotype transformation of human bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular mechanisms...
February 15, 2019: Stem Cell Research & Therapy
Xiaolan Zhu, Huiling Shen, Xinming Yin, Meiling Yang, Hong Wei, Qi Chen, Fan Feng, Yueqin Liu, Wenlin Xu, Yuefeng Li
BACKGROUND: How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. METHODS: The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Fazileh Hosseini Shamili, Houshang Rafatpanah Bayegi, Zahra Salmasi, Kayvan Sadri, Mahmoud Mahmoudi, Mahmoudreza Kalantari, Mohammad Ramezani, Khalil Abnous
Exosomes are biological nano-sized vesicles (~30-200 nm in diameter) that are produced by a wide range of cells and play several roles in cell-cell communications. These vesicles contain membrane and cytoplasmic components of producing cells. Mesenchymal stem cells (MSCs) are the ideal producer of exosomes. The secreted vesicles from MSCs are promising biological vehicles for cell-free therapy in regenerative medicine, cancer therapy and targeted delivery of therapeutic agents to the tumor cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising member of the TNF family with selective effect on cancerous cells...
March 10, 2019: International Journal of Pharmaceutics
Andrea Padoan, Mario Plebani, Daniela Basso
Systemic and local chronic inflammation might enhance the risk of pancreatic ductal adenocarcinoma (PDAC), and PDAC-associated inflammatory infiltrate in the tumor microenvironment concurs in enhancing tumor growth and metastasis. Inflammation is closely correlated with immunity, the same immune cell populations contributing to both inflammation and immune response. In the PDAC microenvironment, the inflammatory cell infiltrate is unbalanced towards an immunosuppressive phenotype, with a prevalence of myeloid derived suppressor cells (MDSC), M2 polarized macrophages, and Treg , over M1 macrophages, dendritic cells, and effector CD4⁺ and CD8⁺ T lymphocytes...
February 5, 2019: International Journal of Molecular Sciences
Yusheng Lin, Hongmei Dong, Weilun Deng, Wan Lin, Kai Li, Xiao Xiong, Yi Guo, Fuyou Zhou, Changchun Ma, Yuping Chen, Hongzheng Ren, Haijun Yang, Ningtao Dai, Lang Ma, Stephen J Meltzer, Sai-Ching J Yeung, Hao Zhang
PURPOSE: Transcriptionally-induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored but convenient and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (se G-N chiRNA) in esophageal squamous cell carcinoma (ESCC)...
February 11, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Feiyu Chen, Ning Wang, Hor-Yue Tan, Wei Guo, Cheng Zhang, Yibin Feng
Cancer is one of the most pervasive causes of morbidity and mortality worldwide regardless of the fact that a majority of therapeutic strategies have been constantly invented. The survival rate of cancer patients remains unsatisfactory due to the late diagnosis, frequent metastasis and poor response to chemotherapeutics. Therefore, novel methods with high specificity and susceptibility for prompt diagnosis and precise treatment of cancer are imperative. Circulating RNA is located in bodily fluids, including urine, saliva, breast milk and naturally present in blood...
February 11, 2019: Cancer Biology & Therapy
Bo Sun, Yiming Zhou, Yantian Fang, Zhenyang Li, Xiaodong Gu, Jianbin Xiang
The lymphatic network remodeling may guide tumor metastasis in a sentinel lymph node (SLN). Although tumor-derived exosomes have been demonstrated to modify the microenvironment in adjacent organs and initiate a pre-metastatic niche, their influence on the lymphatic network in SLNs has not been explained. Here, we show that CT26 cell exosomes (Exo) promote the proliferation of lymphatic endothelial cells and the formation of lymphatic network in SLN, facilitating the SLN metastasis of colorectal cancer (CRC)...
February 8, 2019: International Journal of Cancer. Journal International du Cancer
Haoqi Ni, Su Yang, Felix Siaw-Debrah, Jiangnan Hu, Ke Wu, Zibin He, Jianjing Yang, Sishi Pan, Xiao Lin, Haotuo Ye, Zhu Xu, Fan Wang, Kunlin Jin, Qichuan Zhuge, Lijie Huang
Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient...
2019: Frontiers in Neuroscience
Jingjing Li, Jia Chen, Shaohua Wang, Ping Li, Changli Zheng, Xiao Zhou, Yongguang Tao, Xiang Chen, Lichun Sun, Aijun Wang, Ke Cao, Shijie Tang, Jianda Zhou
There is emerging evidence of bioactive material transport by exosomes in melanoma. However, the functions of exosome content underlying such cancer progression remain largely unknown. We aimed at determining whether exosome secretion contributes to cellular microRNA-494 (miR-494) loss and investigated the roles of miR-494 in melanoma progression. The exosomes from blood serum and cell culture conditioned media were separated by ultracentrifugation. A short hairpin RNA was used to silence rab27a for inhibiting exosome release...
February 5, 2019: Journal of Cellular Physiology
Kavitha Yaddanapudi, Shuhan Meng, Aaron G Whitt, Numan Al Rayyan, Jamaal Richie, Allison Tu, John W Eaton, Chi Li
The antigenic similarity between embryos and tumors has raised the idea of using embryonic material as a preventative vaccine against neoplastic disease. Indeed, we have previously reported that a vaccine comprises allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing GM-CSF (to amplify immune responses) successfully blocks the outgrowth of an implantable cancer (Lewis lung carcinoma; LLC) and lung tumors generated in mice using a combination of a mutagen followed by chronic pulmonary inflammation...
2019: Oncoimmunology
Yamei Shen, Chunling Xue, Xuechun Li, Li Ba, Junjie Gu, Zhao Sun, Qin Han, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) are an important component of the tumor microenvironment, which play an important role in tumor development. Exosomes derived from tumor cells can affect the biological characteristics of MSCs. Our study examined the effects of exosomes derived from gastric cancer cells on MSC immunomodulatory functions. Exosomes were extracted from gastric cancer cell line AGS (AGS-Exos) and cultured with MSCs. MSCs were then co-cultured with both human peripheral blood mononuclear cells (PBMC) and macrophages...
February 4, 2019: Stem Cells and Development
Ryan P McNamara, Pauline E Chugh, Aubrey Bailey, Lindsey M Costantini, Zhe Ma, Rachele Bigi, Avery Cheves, Anthony B Eason, Justin T Landis, Kurtis M Host, Jie Xiong, Jack D Griffith, Blossom Damania, Dirk P Dittmer
Extracellular signaling is a mechanism that higher eukaryotes have evolved to facilitate organismal homeostasis. Recent years have seen an emerging interest in the role of secreted microvesicles, termed extracellular vesicles (EV) or exosomes in this signaling network. EV contents can be modified by the cell in response to stimuli, allowing them to relay information to neighboring cells, influencing their physiology. Here we show that the tumor virus Kaposi's Sarcoma-associated herpesvirus (KSHV) hijacks this signaling pathway to induce cell proliferation, migration, and transcriptome reprogramming in cells not infected with the virus...
February 2019: PLoS Pathogens
Elisabetta Vulpis, Alessandra Soriani, Cristina Cerboni, Angela Santoni, Alessandra Zingoni
Natural killer (NK) cells are innate lymphoid cells that play a pivotal role in tumor surveillance. Exosomes are nanovesicles released into the extracellular environment via the endosomal vesicle pathway and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Moreover, the activation of the DNA damage response (DDR) and the induction of senescence represent two crucial modalities aimed at promoting the clearance of drug-treated tumor cells by NK cells...
January 31, 2019: International Journal of Molecular Sciences
Nongnoot Wongkaew
Cancer diagnostic tools enabling screening, diagnosis, and effective disease management are essential elements to increase the survival rate of diagnosed patients. Low abundance of cancer markers present in large amounts of interferences remains the major issue. Moreover, current diagnostic technologies are restricted to high-resourced settings only. Integrating nanofibers into miniaturized analytical systems holds a significant promise to address these challenges as demonstrated by recent publications. A large surface area, three-dimensional porous network, and diverse range of functional chemistries make nanofibers an excellent candidate as immobilization support and/or transduction elements, enabling high capture yield and ultrasensitive detection in miniaturized devices...
February 1, 2019: Analytical and Bioanalytical Chemistry
Rongkun Li, Yahui Wang, Xiaoxin Zhang, Mingxuan Feng, Jun Ma, Jun Li, Xiaomei Yang, Fang Fang, Qiang Xia, Zhigang Zhang, Mingyi Shang, Shuheng Jiang
BACKGROUND: Lysyl oxidase-like 4 (LOXL4) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). However, the role of LOXL4 in HCC progression remains largely unclear. In this study, we investigated the clinical significance and biological involvement of LOXL4 in the progression of HCC. METHODS: LOXL4 expression was measured in HCC tissues and cell lines. Overexpression, shRNA-mediated knockdown, recombinant human LOXL4 (rhLOXL4), and deletion mutants were applied to study the function of LOXL4 in HCC...
January 31, 2019: Molecular Cancer
Mei-Ling Gao, Fang He, Bin-Cheng Yin, Bang-Ce Ye
An increasing number of studies have found that circulating exosomes play a vital role in the occurrence and metastasis of cancer. Therefore, a direct, sensitive and specific method for detection of tumor exosomes will contribute to the diagnosis and prognosis of cancer. In this work, we take advantage of the facile adaptability of aptamers to design an exosome quantitative method, which converts an exosome capture event to nucleic acid detection. With the help of a hairpin DNA cascade reaction (HDCR) and easy accessibility of DNA dendrimer self-assembly, dual signal amplification was achieved...
January 30, 2019: Analyst
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