Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN

Menck, Kerstin; Scheffold, Christian; Bleckmann, Annalen; Dyck, Lydia; Rost, Ulrike; Wenzel, Dirk; Dhople, Vishnu M.; Siam, Laila; Pukrop, Tobias; Binder, Claudia R.; Klemm, Florian

doi:10.1093/jmcb/mju047

Cited by 116 publications

(145 citation statements)

References 35 publications

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“…In recent years, it has become apparent that metalloproteinases are released directly from the fibroblast plasma membrane in the form of shedding microvesicles . It has also been repeatedly shown that, by doing so, microvesicles affect both matrix invasiveness and cell migration by acting on the integrity of the collagen itself …”

Section: Discussionsupporting

confidence: 53%

Ultrastructural investigation on fibroblast interaction with collagen scaffold

Masci

Taddei

Gambellini

et al. 2015

J Biomedical Materials Res

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Collagen-based scaffolds are used as temporary or permanent coverings to help wound healing. Under natural conditions, wound healing is affected by such factors as cell types, growth factors and several components of the extracellular matrix. Due to the complexity of the cell-to-matrix interaction, many cell based mechanisms regulating wound healing in vivo are not yet properly understood. However, the whole process can be partially simulated in vitro to determine how cells interact with the collagen scaffold in relation to such features as physico-chemical properties, matrix architecture and fiber stability. Under these conditions, cell migration into the collagen matrix can be easily assessed and causally correlated with these features. In this study, we aimed at providing a structural analysis of how NIH3T3 fibroblasts migrate and proliferate in vitro when seeded on a native type-I collagen scaffold. To this end, samples were collected at regular time intervals and analyzed by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Through this experimental approach we demonstrate that collagen is gradually frayed into progressively thinner fibrils as fibroblasts migrate into the matrix, embrace the collagen fibers with long filopodia and form large intracellular vacuoles. A key role in this process is also played by microvesicles shed from the fibroblast plasma membrane and spread over long distances inside the collagen matrix. These observations indicate that a native type-I equine collagen provides favorable conditions for simulating collagen processing in vitro and eventually for unraveling the mechanisms controlling cell uptake and intracellular degradation.

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Section: Discussionsupporting

confidence: 53%

Ultrastructural investigation on fibroblast interaction with collagen scaffold

Masci

Taddei

Gambellini

et al. 2015

J Biomedical Materials Res

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“…Levels of MVs expressing tumor-associated proteins such as MUC1, EGFR or FAK seem to be elevated in the blood of breast cancer patients 15,16 . Also for Exos, recent studies have shown that blood-derived Exos carrying tumor-specific antigens such as Glypican-1 for pancreatic cancer or Del-1 for breast cancer allow early disease detection with high specificity and sensitivity 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Microvesicles from Peripheral Blood

Menck

Bleckmann

Schulz

et al. 2017

JoVE

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The release of extracellular vesicles (EVs) including small endosomal-derived exosomes (Exos, diameter < 100 nm) and large plasma membrane-derived microvesicles (MVs, diameter > 100 nm) is a fundamental cellular process that occurs in all living cells. These vesicles transport proteins, lipids and nucleic acids specific for their cell of origin and in vitro studies have highlighted their importance as mediators of intercellular communication. EVs have been successfully isolated from various body fluids and especially EVs in blood have been identified as promising biomarkers for cancer or infectious diseases. In order to allow the study of MV subpopulations in blood, we present a protocol for the standardized isolation and characterization of MVs from peripheral blood samples. MVs are pelleted from EDTA-anticoagulated plasma samples by differential centrifugation and typically possess a diameter of 100 -600 nm. Due to their larger size, they can easily be studied by flow cytometry, a technique that is routinely used in clinical diagnostics and available in most laboratories. Several examples for quality control assays of the isolated MVs will be given and markers that can be used for the discrimination of different MV subpopulations in blood will be presented.

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Section: Discussionmentioning

confidence: 59%

“…+ taMP and CD147 + EpCAM -MPs were at day 7 post-OP in median not differing compared to respective pre-OP values ( Figure 4C-4D). We speculate that CD147 + EpCAM − MPs were shed from fibroblast, T-cells, stroma cells, epithelial cells during tumour resection indicating tissue remodelling, migration and cancer cell invasion in which EMMPRIN/CD147 might play role as suggested by others [7,20,21].Taken together, in vivo cancer cells shed distinct taMP populations with a unique pan-cancer MPs-based signature. Even if each tumour is composed of a mixture of heterogeneous tumour cells, the released EpCAM + and EpCAM + CD147 + taMPs can be reliable detected in the circulation in both primary and metastatic tumour-bearing patients ( Figure 4E).…”

mentioning

confidence: 59%

Tumour-associated circulating microparticles: a novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia

et al. 2016

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Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the socalled liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM Oncotarget 30868 www.impactjournals.com/oncotarget apoptosis and that are released into the extracellular space. MPs can be isolated from human fluids such as whole blood, plasma, serum or e.g. synovial fluid [1][2][3][4][5][6]. They carry the surface signature of their cell of origin and the quantification of MP subsets using FACS sorting permits a non-invasive assessment of cell specific pathologies, especially in inflammation [7][8][9][10]. MPs have to be differentiated and separated from exosomes, which are derived from intracellular vesicles and do not carry cell surface markers of their origin, and from the larger fragments of apoptotic bodies [2,3]. So far, only a few and technically limited studies have been performed on putative cancer-derived MPs or microvesicles identified by single surface marker [11][12][13]. Therefore, we explored the diagnostic potential of tumour-associated MPs (taMPs) and MP subtypes in thoroughly characterised patients with various underlying cancer entities such as colorectal carcinoma, non-small cell lung carcinoma and pancreas carcinoma. RESULTS Patients with CRC, other neoplasia or thyroid nodules (struma nodosa) show characteristic MP profilesBased on literature research various cancer markers were considered for the detection of taMPs expressing common cancer antigens as EpCAM and CD147. Corresponding cancer lines were screened for the chosen surface antigens (data not shown). Indeed, EpCAM and CD147 were identified on the surface of cancer cell lines of colorectal (CRC), lung (NSCLC) and pancreas (PaCa) (data not shown). MPs were isolated by differential centrifugation of sera of total 103 confirmed cancer patients. Median EpCAM + taMPs values were significantly elevated (oneway ANOVA) in patients with CRC (n = 52), NSCLC (n = 40), PaCa (n = 11) by an average of 2.3 fold irrespective of the tumour entity and size ( Figure 1A and Table 1). Surprisingly, EpCAM + taMPs were also found elevated in thyroid nodules patients (short: struma, n = 40) as compared to healthy controls by 1.9 fold (p < 0.05). Nevertheless, the antigen combination of EpC...

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Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN

Cited by 116 publications

References 35 publications

Ultrastructural investigation on fibroblast interaction with collagen scaffold

Ultrastructural investigation on fibroblast interaction with collagen scaffold

Isolation and Characterization of Microvesicles from Peripheral Blood

Tumour-associated circulating microparticles: a novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia

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