Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles

Lima, Luize Gonçalves; Leal, Ana Carolina; Vargas, Gabriele; Porto-Carreiro, Isabel; Monteiro, Robson Q.

doi:10.1016/j.thromres.2013.07.026

Cited by 47 publications

(33 citation statements)

References 50 publications

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“…Notably, the secreted Zinc-ZFP-GST NPs from zinc-treated cells are naturally enclosed in MVs. MVs are fragments of the plasma membrane-derived liposome that are shed from almost all cell types under normal or pathological conditions3334. To date, MVs have been mainly studied by biological methods, which remains challenging due to their comparatively small size of 50–100 nm.…”

Section: Discussionmentioning

confidence: 99%

Multicolor bioimaging with biosynthetic zinc nanoparticles and their application in tumor detection

Kang

et al. 2017

Sci Rep

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Because they generate excellent images, nanoparticles (NPs), especially biosynthesized NPs, provide a new solution for tumor imaging. In this research, we unveil a novel type of biosynthesized NPs featuring multicolor fluorescence. These NPs exhibit little cytotoxicity to cells. The explored NPs, designated Zn-ZFP-GST NPs (Zinc NPs in abbreviation), are generated from leukemia cells treated with a Zn2+ solution, while zinc-finger protein and glutathione S-transferase (GST) were also identified in the Zinc NPs. Under near-UV illumination, the Zinc NPs simultaneously emit green, yellow, and red fluorescence. In addition, the intensity of the fluorescence increases with the existence of sulfides. Besides, the NPs are encapsulated by microvesicles (MVs) shed from the plasma membrane. As observed in whole-body research of nude mice, the NP-MVs migrate via blood circulation and are distinguished by their fluorescent signals. Furthermore, the folic acid (FA) & AVR2 (human VEGF antibody)-coated NP-MVs are exploited to target the tumor location, and the feasibility of this approach has been confirmed empirically. The Zinc NPs shed light on an alternative solution to tumor detection.

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Section: Discussionmentioning

confidence: 99%

Multicolor bioimaging with biosynthetic zinc nanoparticles and their application in tumor detection

Kang

et al. 2017

Sci Rep

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“…This process triggers a proangiogenic cascade dependent on PAR2 signaling in endothelial cells that in turn results in an increase in PAR2 expression upon hypoxia (32). In addition, TF-containing MVs may promote TF transfer between tumor cell lines with different aggressive behaviors, thus, modulating their procoagulant properties (41).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

et al. 2016

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Abstract. Hypoxia and necrosis are fundamental features of glioma, and their emergence is critical for the rapid biological progression of this fatal tumor. The presence of vaso-occlusive thrombus is higher in grade IV tumors [glioblastoma multiforme (GBM)] compared with lower grade tumors, suggesting that the procoagulant properties of the tumor contribute to its aggressive behavior, as well as the establishment of tumor hypoxia and necrosis. Tissue factor (TF), the primary cellular initiator of coagulation, is overexpressed in GBMs and likely favors a thrombotic microenvironment. Phosphatase and tensin homolog (PTEN) loss and hypoxia are two common alterations observed in glioma that may be responsible for TF upregulation. In the present study, ST1 and P7 rat glioma lines, with different levels of aggressiveness, were comparatively analyzed with the aim of identifying differences in procoagulant mechanisms. The results indicated that P7 cells display potent procoagulant activity compared with ST1 cells. Flow cytometric analysis showed less pronounced levels of TF in ST1 cells compared with P7 cells. Notably, P7 cells supported factor X (FX) activation via factor VIIa, whereas no significant FXa generation was observed in ST1 cells. Furthermore, the exposure of phosphatidylserine on the surface of P7 and ST1 cells was investigated. The results supported the assembly of prothrombinase complexes, accounting for the production of thrombin. Furthermore, reverse transcription-quantitative polymerase chain reaction showed that CoCl 2 (known to induce a hypoxic-like stress) led to an upregulation of TF levels in P7 and ST1 cells. Therefore, increased TF expression in P7 cells was accompanied by increased TF procoagulant activity. In addition, hypoxia increased the shedding of procoagulant TF-bearing microvesicles in both cell lines. Finally, hypoxic stress induced by treatment with CoCl 2 upregulated the expression of the PAR1 receptor in both P7 and ST1 cells. In addition to PAR1, P7, but not ST1 cells, expressed higher levels of PAR2 under hypoxic stress. Thus, modulating these molecular interactions may provide additional insights for the development of more efficient therapeutic strategies against aggressive glioma.

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“…Reciprocally, there is a growing body of evidence that complex interactions between tumor cells and circulating platelets play an important role regulating tumor growth, dissemination and angiogenesis 8–10. Platelet-derived microparticles (PMPs) also share a pathological function in this complex interaction 55,56…”

Section: Platelets and Platelets-derived Microparticlesmentioning

confidence: 99%

“…Oncogenic pathways also stimulate production of MP/MV harboring tissue factor (TF) that contributes to cancer-induced thrombosis 76. MP also correlates with processes related to cell aggressiveness including primary tumor growth, invasion, and metastasis 77. TF-bearing MV can be transferred between different populations of cancer cells and may therefore contribute to the propagation of the aggressive phenotype among heterogeneous subsets of cells in a tumor 77…”

Section: Platelets and Platelets-derived Microparticlesmentioning

confidence: 99%

Regulation of Tumor Growth and Metastasis: The Role of Tumor Microenvironment

Goubran

Kotb

Stakiw

et al. 2014

Cancer�Growth�Metastasis

170

126

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The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body’s immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor’s surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

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Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles

Cited by 47 publications

References 50 publications

Multicolor bioimaging with biosynthetic zinc nanoparticles and their application in tumor detection

Multicolor bioimaging with biosynthetic zinc nanoparticles and their application in tumor detection

Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

Regulation of Tumor Growth and Metastasis: The Role of Tumor Microenvironment

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