Breast Cancer Exosome-like Microvesicles and Salivary Gland Cells Interplay Alters Salivary Gland Cell-Derived Exosome-like Microvesicles In Vitro

Lau, Chang Shun; Wong, David T.

doi:10.1371/journal.pone.0033037

Cited by 91 publications

(79 citation statements)

References 24 publications

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“…Tumor-specific EGFRvIII can be released into the blood to merge with the plasma membranes of cancer cells that lack EGFRvIII (27), and cancer-derived microvesicles can alter the contents of secreted microvesicles of salivary gland cells (28). We therefore hypothesized that an EGFR mutation could be detected in the plasma and saliva of patients with NSCLC.…”

Section: Efirm Detection Of Egfr Mutations In Plasma and Saliva From mentioning

confidence: 99%

Noninvasive Saliva-based EGFR Gene Mutation Detection in Patients with Lung Cancer

Fang¹,

Lin

Joon

et al. 2014

Am J Respir Crit Care Med

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153

151

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Rationale: Constitutive activation of the epidermal growth factor receptor (EGFR) is prevalent in epithelial cancers, particularly in non-small cell lung carcinoma (NSCLC). Mutations identified in EGFR predict the sensitivity to EGFR-targeted therapy. Detection of these mutations is mainly based on tissue biopsy, which is invasive, expensive, and time consuming.Objectives: Noninvasive, real-time, inexpensive detection and monitoring of EGFR mutations in patients with NSCLC is highly desirable.Methods: We developed a novel core technology, electric field-induced release and measurement (EFIRM), which relies on a multiplexible electrochemical sensor that can detect EGFR mutations directly in bodily fluids.Measurements and Main Results: We established EFIRM for the detection of the EGFR mutations in vitro and correlated the results with tumor size from xenografted mice. In clinical application, we demonstrated that EFIRM could detect EGFR mutations in the saliva and plasma of 22 patients with NSCLC. Finally, a blinded test was performed on saliva samples from 40 patients with NSCLC. The receiver operating characteristic analysis indicated that EFIRM detected the exon 19 deletion with an area under the curve of 0.94 and the L858R mutation with an area under the curve of 0.96.Conclusions: Our data indicate that EFIRM is effective, accurate, rapid, user-friendly, and cost effective for the detection of EGFR mutations in the saliva of patients with NSCLC. We termed this saliva-based EGFR mutation detection (SABER).

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Section: Efirm Detection Of Egfr Mutations In Plasma and Saliva From mentioning

confidence: 99%

Noninvasive Saliva-based EGFR Gene Mutation Detection in Patients with Lung Cancer

Fang¹,

Lin

Joon

et al. 2014

Am J Respir Crit Care Med

Self Cite

153

151

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“…16 Compared to the overall prevalence of breast cancer, a limited number of reports have indicated exosomes and/or microvesicles to be of relevance in breast cancer. [17][18][19] The focus, however, has typically been on HER2-overexpressing cells and their exosomes. Here, in what we believe to be the first study specifically considering exosomes in the context of TNBC, we have included analysis of exosomes from the claudin-low TNBC cell line Hs578T 20 and its isogenic subclone, Hs578Ts(i) 8 , 21 as well as exosomes from TNBC patients compared to healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

O’Brien

Rani

Corcoran

et al. 2013

European Journal of Cancer

197

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Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i) 8 variant, as well as exosomes from TNBC patient sera compared to normal sera. Methods: Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i) 8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/ recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. Results: Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i) 8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i) 8 -exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i) 8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our 0959-8049/$ -see front matter Ó

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“…It was reported that breast cancer exosome-like microvesicles altered the protein and mRNA compositions of exosome-like vesicles derived from salivary glands. 14) In addition, in patients with oral lichen planus, a chronic inflammatory oral mucosal disease, miR-4484 levels in salivary exosomes were significantly increased. 15) Because exosomes have pathophysiological significance, it is important to elucidate their stability under various conditions in the oral cavity, digestive tract and plasma.…”

mentioning

confidence: 99%

Characterization of Membrane Integrity and Morphological Stability of Human Salivary Exosomes

Kumeda

Ogawa

Akimoto³

et al. 2017

Biological & Pharmaceutical Bulletin

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Exosomes are derived from various sources, including primary and cultured cell lines and body fluids. It is now evident that they are important for communication between cells. They have, therefore, been proposed as potential carriers to deliver drugs to specific sites. In this study, we examined stability of exosomes derived from human saliva. Exosomes were stored at 4°C for up to 20 months and their membrane integrity assessed. Several exosomal markers, such as dipeptidyl peptidase IV (DPP IV; membrane marker) and programmed cell death 6-interacting protein (Alix, lumen marker), were retained intact after 20 months storage at 4°C. Moreover, intact exosomes could be isolated from whole saliva that had been stored at 4°C. Membrane disruption with detergents such as Triton X-100 and Nonidet P-40 caused partial solubilization of DPP IV and release of Alix into the supernatant. In contrast, sodium dodecyl sulfate treatment caused a complete disruption of the membrane. In addition, membrane stability was maintained after freezing and thawing. These results indicated that human saliva-derived exosomes are stable, maintaining their membrane integrity over a long storage period.

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Breast Cancer Exosome-like Microvesicles and Salivary Gland Cells Interplay Alters Salivary Gland Cell-Derived Exosome-like Microvesicles In Vitro

Cited by 91 publications

References 24 publications

Noninvasive Saliva-based EGFR Gene Mutation Detection in Patients with Lung Cancer

Noninvasive Saliva-based EGFR Gene Mutation Detection in Patients with Lung Cancer

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

Characterization of Membrane Integrity and Morphological Stability of Human Salivary Exosomes

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