Cancer-associated thrombosis is one of the major causes of worse prognosis among tumor-bearing patients. Extracellular vesicles derived from cancer cells, which can be divided mainly into ...microvesicles and exosomes, can participate in several tumor progression phenomena. Tumor-derived microvesicles positive for tissue factor (TF) have been associated with thrombotic risk in certain cancer types. Cancer cell-derived exosomes, however, have not. In this study we evaluated the capacity of extracellular vesicles (EVs, containing both microvesicles and exosomes) derived from breast-cancer cell lines in promoting platelet activation, aggregation and plasma coagulation, in experiments that access both TF-dependent and -independent activities.
EVs were isolated from the conditioned media of two human mammary carcinoma cell lines: MDA-MB-231 (highly invasive) and MCF-7 (less invasive). TF-independent EV/platelet interaction, platelet P-selectin exposure and aggregation were evaluated. Western blotting, plasma clotting and platelet aggregation in the presence of plasma were performed for the measurement of TF-dependent activity in EVs.
Interaction between MDA-MB-231 EVs and washed platelets led to increased platelet P-selectin exposure and platelet aggregation compared to MCF-7 EVs. MDA-MB-231 EVs had higher TF protein levels and TF-dependent procoagulant activity than MCF-7 EVs. Consequently, TF-dependent platelet aggregation was also induced by MDA-MB-231 EVs, but not by MCF-7 EVs.
Our results suggest that MDA-MB-231 EVs induce TF-independent platelet activation and aggregation, as well as TF-dependent plasma clotting and platelet aggregation by means of thrombin generation. In this context, aggressive breast cancer-derived EVs may contribute to cancer-associated thrombosis.
•Extracellular vesicles (EVs) derived from breast cancer cell lines interact with platelets.•MDA-MB-231 EVs induce TF-independent platelet activation and aggregation.•MDA-MB-231 EVs induce TF-dependent plasma clotting.•Thrombin generated by MDA-MB-231 EVs promotes platelet aggregation in plasma.•MCF-7 EVs were very much less efficient in eliciting pro-hemostatic responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, ...and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant ( E -value > 0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E -value = zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral proteins (as Ras, Akt and EGFR) can elicit the same phenotype. Furthermore, a corollary to this hypothesis presumes that target-directed anti-cancer therapy should target human protein domains of low similarity to prokaryotic homologs for a well-succeeded anti-cancer therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The main goal of this work was to evaluate the therapeutic potential of green superparamagnetic iron oxide nanoparticles (SPIONs) produced with coconut water for treating cutaneous leishmaniasis ...caused by
Leishmania amazonensis
. Optical and electron microscopy techniques were used to evaluate the effects on cell proliferation, infectivity percentage, and ultrastructure. SPIONs were internalized by both parasite stages, randomly distributed in the cytosol and located mainly in membrane-bound compartments. The selectivity index for intracellular amastigotes was more than 240 times higher compared to current drugs used to treat the disease. The synthesized SPIONs showed promising activity against
Leishmania
and can be considered a strong candidate for a new therapeutic approach for treating leishmaniases.
Aims
Immobilization of microbial cells is a useful strategy for developing high cell density bioreactors with improved stability and productivity for production of different chemicals. ...Functionalization of the immobilization matrix or biofilm forming property of some strains has been utilized for achieving cell attachment. The aim of the present study was to investigate the production of exopolysaccharide (EPS) by Propionibacterium freudenreichii C.I.P 59.32 and utilize this feature for immobilization of the cells on porous glass beads for production of propionic acid.
Methods and Results
Propionibacterium freudenreichii was shown to produce both capsular and excreted EPS during batch cultivations using glucose as carbon source. Different electron microscopy techniques confirmed the secretion of EPS and formation of cellular aggregates. The excreted EPS was mainly composed of mannose and glucose in a 5·3 : 1 g g−1 ratio. Immobilization of the cells on untreated and polyethyleneimine (PEI)‐treated Poraver beads in a bioreactor was evaluated. Higher productivity and yield of propionic acid (0·566 g l−1 h−1 and 0·314 g g−1, respectively) was achieved using cells immobilized to untreated beads and EPS production reached 617·5 mg l−1 after 48 h.
Conclusion
These results suggest an important role of EPS‐producing strains for improving cell immobilization and propionic acid production.
Significance and Impact of the Study
This study demonstrates the EPS‐producing microbe to be easily immobilized on a solid matrix and to be used in a bioprocess. Such a system could be optimized for achieving high cell density in fermentations without the need for functionalization of the matrix.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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