Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells

Zara, M; Canobbio, Ilaria; Visconte, Caterina; Canino, Jessica; Torti, Mauro; Guidetti, Gianni Francesco

doi:10.1016/j.cellsig.2018.04.008

Cited by 64 publications

(42 citation statements)

References 31 publications

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“…However, ITGA2B shows to be particularly enriched in platelet, non-small cell lung cancer cells (ProteomicsDB), and basophils (Human Protein Atlas). The presence of circulating ITGA2B may indicate an ongoing process of tumor cell-induced platelet aggregation [29].…”

Section: Discussionmentioning

confidence: 99%

Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

et al. 2020

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Background The lack of specificity and high degree of false positive and false negative rates when using mammographic screening for detecting early-stage breast cancer is a critical issue. Blood-based molecular assays that could be used in adjunct with mammography for increased specificity and sensitivity could have profound clinical impact. Our objective was to discover and independently verify a panel of candidate blood-based biomarkers that could identify the earliest stages of breast cancer and complement current mammographic screening approaches. Methods We used affinity hydrogel nanoparticles coupled with LC-MS/MS analysis to enrich and analyze low-abundance proteins in serum samples from 20 patients with invasive ductal carcinoma (IDC) breast cancer and 20 female control individuals with positive mammograms and benign pathology at biopsy. We compared these results to those obtained from five cohorts of individuals diagnosed with cancer in organs other than breast (ovarian, lung, prostate, and colon cancer, as well as melanoma) to establish IDC-specific protein signatures. Twenty-four IDC candidate biomarkers were then verified by multiple reaction monitoring (LC-MRM) in an independent validation cohort of 60 serum samples specifically including earliest-stage breast cancer and benign controls (19 early-stage (T1a) IDC and 41 controls). Results In our discovery set, 56 proteins were increased in the serum samples from IDC patients, and 32 of these proteins were specific to IDC. Verification of a subset of these proteins in an independent cohort of early-stage T1a breast cancer yielded a panel of 4 proteins, ITGA2B (integrin subunit alpha IIb), FLNA (Filamin A), RAP1A (Ras-associated protein-1A), and TLN-1 (Talin-1), which classified breast cancer patients with 100% sensitivity and 85% specificity (AUC of 0.93). Conclusions Using a nanoparticle-based protein enrichment technology, we identified and verified a highly specific and sensitive protein signature indicative of early-stage breast cancer with no false positives when assessing benign and inflammatory controls. These markers have been previously reported in cell-ECM interaction and tumor microenvironment biology. Further studies with larger cohorts are needed to evaluate whether this biomarker panel improves the positive predictive value of mammography for breast cancer detection.

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Section: Discussionmentioning

confidence: 99%

Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

et al. 2020

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“…9 Activation of the extrinsic pathway is mainly due to tumor-derived, tissue factor-positive (TF þ ) extracellular vesicles (EVs), while activation of intrinsic pathway is due to neutrophil extracellular traps and/or polyphosphate P. 9 On the other hand, tumor cell-induced platelet aggregation and activation have been demonstrated in several cancer types. 10 Finally, hypofibrinolysis due to tumor-increased expression of plasminogen activator inhibitor-1 (PAI-1) has also been described. 11 As far as ambulatory cancer patients are specifically concerned, the main pathophysiological mechanisms of hypercoagulability to consider are ongoing chemotherapy and or/radiotherapy, presence of indwelling peripheral or central venous catheters, antiangiogenesis, hormonal or erythropoiesis-stimulating agents, and red blood cell or platelet transfusions (►Table 1).…”

Section: Pathophysiology Of Cancer-associated Thrombosis In Ambulatormentioning

confidence: 99%

Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy: Risk Factors and Prevention

Prandoni¹,

Campello

2021

Semin Thromb Hemost

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Ambulatory cancer patients undergoing chemotherapy are at a substantial risk for venous thromboembolism (VTE) over the course of therapy and beyond it. Factors accounting for this risk include the activation of extrinsic and intrinsic coagulation pathways, platelet activation, impaired fibrinolysis, use of catheters, infusion of blood products, and thrombogenic potential of several chemotherapeutic drugs. A few stratification models can help identify patients at a higher risk of chemotherapy-associated VTE, who may benefit from preventive strategies. Although low-molecular-weight heparins (LMWHs) effectively reduce the risk of VTE, current guidelines recommend against their routine use. Based on the results of recent randomized controlled clinical trials, the administration of prophylactic doses of the novel direct oral anticoagulants (DOACs) to ambulatory cancer patients undergoing chemotherapy has the potential to offer an effective and safe protection against VTE, obviating the inconveniences of heparins. Except for patients in whom the novel drugs are unsuitable or are contraindicated, in all other patients LMWHs should be replaced by low-dose DOACs.

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“…In particular, the extracellular N-terminus of PARs, such as PAR-1 and PAR-3, which are expressed by cancer cells and also CAFs, can be canonically cleaved by thrombin and also non-canonically by certain MMPs, such as MMP-1 and MMP-13 [407][408][409]. Canonically, thrombin is secreted by activated monocytes/macrophages in the tumor stroma and activated by the extrinsic coagulation cascade that is triggered by the tissue factor (TF) that is usually expressed on cancer cells [410]. Non-canonically, MMPs proteolytically activate the Gα12/13 of the heterotrimeric G protein and thus Rho signaling.…”

Section: Mmps Promote Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

Niland

Eble

2020

IJMS

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The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.

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Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells

Cited by 64 publications

References 31 publications

Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy: Risk Factors and Prevention

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

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