Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett

Tumor Immunology Programme, D015, German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
Cancer letters (Impact Factor: 5.62). 02/2009; 278(1):73-81. DOI: 10.1016/j.canlet.2008.12.028
Source: PubMed


Exosomes are membrane vesicles that are released from many different cell types. Tumor derived-exosomes play a role in immune suppression. We hypothesized that in ovarian carcinoma patients exosomes initially produced at the local abdominal site may become systemic. We examined paired samples of ascites and blood from ovarian carcinoma patients for the presence of exosomes. We also studied the requirements for exosomal uptake by immune cells, the role of phosphatidyl-serine (PS) as uptake signal and the effect of exosome application on tumor growth. We used exosomes from ovarian carcinoma cell lines, malignant ascites and sera from ovarian carcinoma patients isolated by ultracentrifugation. PS-displayed by exosomes was detected by Anexin-V-FITC staining of latex beads adsorbed exosomes. For uptake experiments, labeled exosomes were exposed to cells in the presence or absence of cold Annexin-V as competitor. Uptake was examined by fluorescent microscopy and cytofluorographic analysis. Effects of exosomes on tumor growth were studied using SKOV3ip ovarian carcinoma cells in CD1 nu/nu mice. We found that malignant ascites-derived exosomes cargo tumor progression related proteins such as L1CAM, CD24, ADAM10, and EMMPRIN. We observed that exosomes become systemic via the blood stream. Uptake of ovarian carcinoma exosomes by NK cells was found to require PS at the exosomal surface but the presence of PS was not sufficient. Application of malignant ascites-derived exosomes to tumor bearing mice resulted in augmented tumor growth. Exosomes from the serum of tumor patients could be isolated from only one ml of blood and this analysis could serve for diagnostic purposes. We propose that tumor-derived exosomes could play a role in tumor progression.

28 Reads
  • Source
    • "For example, cancer cells secrete exosomes that appear capable of inducing oncogenic properties in recipient cells, including increased cell division or metastatic behaviour [28] [29] [30]. Consistent with findings that exosome levels are raised in the blood of cancer patients [29] [31], exosome-mediated signalling may underlie the cancer 'field effect', in which tumour cells have been shown to influence the phenotype of nearby cells [32]. Only recently light has been shed on the subcellular compartments and mechanisms involved in their biogenesis and secretion opening new avenues to understand their functions [27]. "
    [Show description] [Hide description]
    DESCRIPTION: Exosomes, ionising radiation, non-targeted effects of ionising radiation
  • Source
    • "Multiple dilutions in PBS and centrifugations 100,000 × g, 70 min 2. sucrose cushion (Rani et al. 2011) Fraction in density gradient 1.07–1.18 g/ml (Heijnen et al. 1999, Thery et al. 2001, Keller et al. 2009, Tauro et al. 2012) Unspecified 1.24–1.28 g/ml (Thery et al. 2001) Unspecified "
    [Show abstract] [Hide abstract]
    ABSTRACT: The release of extracellular vesicles (EVs), including exosomes and microvesicles, is a phenomenon shared by many cell types as a means of communicating with other cells and also potentially removing cell contents. The cargo of EVs includes the proteins, lipids, nucleic acids, and membrane receptors of the cells from which they originate. EVs released into the extracellular space can enter body fluids and potentially reach distant tissues. Once taken up by neighboring and/or distal cells, EVs can transfer functional cargo that may alter the status of recipient cells, thereby contributing to both physiological and pathological processes. In this article, we will focus on EV composition, mechanisms of uptake, and their biological effects on recipient cells. We will also discuss established and recently developed methods used to study EVs, including isolation, quantification, labeling and imaging protocols, as well as RNA analysis.
    BioScience 07/2015; 65(783). DOI:10.1093/biosci/biv084 · 5.38 Impact Factor
    • "Promote tumor grow in vivo [26] GG, SKOV-3, M130 cells and ascites of ovarian cancer patients Differential centrifugation Sucrose-density gradient centrifugation and Western blot Express gelatinolytically active protein that may degrade extracellular matrix [20] OVMz and SKOV-3ip cells Differential centrifugation Sucrose-density gradient centrifugation and Western blot Express proteolytically active ADAM10 and ADAM17 and mediate ectodomain cleavage of L1 and CD44 [21] OVMz and ascites of ovarian cancer patients "
    [Show abstract] [Hide abstract]
    ABSTRACT: The limitations of current chemotherapies have motivated research in developing new treatments. Growing evidences show that interaction between tumors and their microenvironment, but not tumor cells per se, is the key factor in tumor progression and therefore of obvious scientific interest and therapeutic value. Exosomes are small (30 to 100 nm) extracellular vesicles which have emerged as key mediators and communicators between cancer cells and other major cell types in the tumor microenvironment such as stromal fibroblasts, endothelial cells, and infiltrating immune cells as well as noncellular extracellular matrices through paracrine mechanisms. This review is to highlight the emerging role of exosomes in particular type of cancer, such as ovarian cancer, owing to its unique route of metastasis, which is capable of rapidly translating exosome research for clinical applications in diagnosis, prognosis, and potential treatment. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 07/2015; 367(1). DOI:10.1016/j.canlet.2015.07.014 · 5.62 Impact Factor
Show more