Release of Prometastatic Platelet-Derived Microparticles Induced by Breast Cancer Cells: A Novel Positive Feedback Mechanism for Metastasis

Zara, M; Guidetti, Gianni Francesco; Boselli, Daniela; Villa, Chiara; Canobbio, Ilaria; Seppi, Claudio; Visconte, Caterina; Canino, Jessica; Torti, Mauro

doi:10.1055/s-0037-1613674

Cited by 24 publications

(29 citation statements)

References 25 publications

(35 reference statements)

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“…Washed human platelets were prepared from buffy‐coat bags collected the same day of the experiment, a previously described 23 . Briefly, the buffy‐coat was diluted with one‐fourth of its initial volume using a 9:1 solution of 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) buffer (10 mmol/L HEPES, 137 mmol/L NaCl, 2.9 mmol/L KCl, 12 mmol/L NaHCO3, pH 7.4) and citric acid/citrate/dextrose (152 mmol/L sodium citrate, 130 mmol/L citric acid, and 112 mmol/L glucose) and centrifuged at 120 g for 15 minutes.…”

Section: Methodsmentioning

confidence: 99%

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Fibrillar amyloid peptides promote platelet aggregation through the coordinated action of ITAM‐ and ROS‐dependent pathways

Visconte

Canino

Vismara

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Amyloid peptides Aβ40 and Aβ42, whose deposition in brain correlates with Alzheimer disease, are also present in platelets and have prothrombotic activities. Objective: In this study, we analyze the ability of Aβ peptides to form fibrils and to induce platelet activation and aggregation. Methods: Aβ40, Aβ42, and their scrambled peptides were diluted in phosphate buffered saline and fibrillogenesis was investigated by ThioflavinT and Congo Red. Aggregation, protein phosphorylation, and reactive oxygen species (ROS) production were analyzed. Results: Aβ40 and Aβ42, but not scrambled peptides, were able to form fibrils when diluted in phosphate buffered saline. Fibrillogenesis of Aβ42 was very rapid, whereas fibril formation by Aβ40 was completed only after 48 hours of incubation. Fibrillar Aβ40 and Aβ42 promoted dose-dependent aggregation of washed platelets in the presence of extracellular CaCl 2. Cleavage of GPIbα by mocarhagin or blockade of the ITAM-containing FcγRIIA prevented platelet aggregation induced by fibrillary Aβ40 and Aβ42. Fibrillar Aβ peptides stimulated the phosphorylation of FcγRIIA, resulting in the downstream stimulation of PLC, protein kinase C, and phosphoinositide 3-kinases, whose activity was necessary for full aggregation of platelets. Fibrillar Aβ peptides also induced ROS generation, and NOX inhibitors, as well as ROS scavengers, prevented platelet aggregation. However, Aβ peptide-induced ROS production did not require binding to GPIbα or activation of FcγRIIA, but was initiated by CD36, which provided an important contribution to full platelet aggregation. Conclusion: These results suggest that fibrillar amyloid Aβ40 and Aβ42 induce platelet aggregation through the recruitment of GPIb-IX-V and CD36, which requires the convergence of ITAM-and ROS-dependent pathways.

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Section: Methodsmentioning

confidence: 99%

“…Washed human platelets were prepared from buffy-coat bags collected the same day of the experiment, a previously described. 23 Briefly, the buffy-coat was diluted with one-fourth of its initial volume using…”

Section: Human Platelet Preparationmentioning

confidence: 99%

Fibrillar amyloid peptides promote platelet aggregation through the coordinated action of ITAM‐ and ROS‐dependent pathways

Visconte

Canino

Vismara

et al. 2020

Journal of Thrombosis and Haemostasis

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“…Noteworthy, a bidirectional effect occurs as cancer cells can induce platelet activation and MV release; subsequently, a paracrine positive feedback mechanism is established, since MVs, taken up by cancer cells, potentiate the invasive phenotype through stimulation of migration [148,155]. Interestingly, although different cancer cells are able to induce platelet-derived MV release, only the most aggressive ones are responsive to MV action and, furthermore, only some subsets of MVs can positively feed back to cancer cells [155]. These findings suggest that i) cancer/platelet interplay is complex and strongly dependent on features of tumor cell type and ii) composition of MVs may differ depending on the stimulus given to platelets [155].…”

Section: Platelet Microvesicle-derived Mirnasmentioning

confidence: 99%

“…Interestingly, although different cancer cells are able to induce platelet-derived MV release, only the most aggressive ones are responsive to MV action and, furthermore, only some subsets of MVs can positively feed back to cancer cells [155]. These findings suggest that i) cancer/platelet interplay is complex and strongly dependent on features of tumor cell type and ii) composition of MVs may differ depending on the stimulus given to platelets [155]. These findings may clarify discrepancies observed by authors in studies using different platelet preparations, agonists and cancer cell types.…”

Section: Platelet Microvesicle-derived Mirnasmentioning

confidence: 99%

The “Janus Face” of Platelets in Cancer

Catani

Savini

Tullio

et al. 2020

IJMS

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Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

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“…Another interesting issue is the ability of cancer cells to educate PLTs. Zarà et al demonstrated that breast cancer cell lines—highly aggressive MDM-MB-231 and MCF7 could educate PLTs to produce PEVs in an amount similar to that after thrombin activation [ 96 ]. Next, those PEVs were co-cultured with cancer cells to investigate if the newly formed PEVs impact cells.…”

Section: Pevs In Cancer Progressionmentioning

confidence: 99%

Platelets Extracellular Vesicles as Regulators of Cancer Progression—An Updated Perspective

Żmigrodzka

Winnicka

2020

IJMS

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Extracellular vesicles (EVs) are a diverse group of membrane-bound structures secreted in physiological and pathological conditions by prokaryotic and eukaryotic cells. Their role in cell-to-cell communications has been discussed for more than two decades. More attention is paid to assess the impact of EVs in cancer. Numerous papers showed EVs as tumorigenesis regulators, by transferring their cargo molecules (miRNA, DNA, protein, cytokines, receptors, etc.) among cancer cells and cells in the tumor microenvironment. During platelet activation or apoptosis, platelet extracellular vesicles (PEVs) are formed. PEVs present a highly heterogeneous EVs population and are the most abundant EVs group in the circulatory system. The reason for the PEVs heterogeneity are their maternal activators, which is reflected on PEVs size and cargo. As PLTs role in cancer development is well-known, and PEVs are the most numerous EVs in blood, their feasible impact on cancer growth is strongly discussed. PEVs crosstalk could promote proliferation, change tumor microenvironment, favor metastasis formation. In many cases these functions were linked to the transfer into recipient cells specific cargo molecules from PEVs. The article reviews the PEVs biogenesis, cargo molecules, and their impact on the cancer progression.

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Release of Prometastatic Platelet-Derived Microparticles Induced by Breast Cancer Cells: A Novel Positive Feedback Mechanism for Metastasis

Cited by 24 publications

References 25 publications

Fibrillar amyloid peptides promote platelet aggregation through the coordinated action of ITAM‐ and ROS‐dependent pathways

Fibrillar amyloid peptides promote platelet aggregation through the coordinated action of ITAM‐ and ROS‐dependent pathways

The “Janus Face” of Platelets in Cancer

Platelets Extracellular Vesicles as Regulators of Cancer Progression—An Updated Perspective

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