ReviewPlatelet microparticles and cancer: An intimate cross-talk
Introduction
The complex relationship between cancer and thrombosis has long been established since the late 19th century by Armand Trousseau, who highlighted that thrombophlebitis is a premonitory sign of occult malignancy [1]. Venous thromboembolism (VTE) occurs in 15–20% of patients with cancer [2]. In some cancers, thromboembolic diseases are the second most common cause of death, accounting for 44% of deaths after the progression of the cancer itself [3], [4].
Multiple studies focused on the role played by coagulation, tissue factor and platelets and their generated microparticles (PMPs) in the context of cancer, inducing thrombosis [5], [6], [7]. Reciprocally, platelets and their MPs seem to interact with tumors favoring their progression and dissemination. A complex bidirectional relationship therefore exists between the platelets (and the microparticles, MPs) on one hand and tumors on the other [8].
Section snippets
Platelet microparticle generation by tumors
PMPs shed from platelets after physiological activation by agonists like thrombin or collagen [9], [10]. The shed microparticles are endowed with procoagulant properties as they may harbor phosphatidylserine and tissue factor, the major initiator of blood coagulation reactions [11]. Platelet activation, and hence PMP generation, has been described in the context of occult and overt malignancy in the presence or absence of distant spread. Tumor cell-induced platelet aggregation (TCIPA) is a
Effect of PMPs on cancer growth, tethering and spread
If cancer cells are capable of inducing PMP generation through the activation of platelets via multiple mechanisms, reciprocally, PMPs are capable of interacting significantly with tumors through a multitude of direct and indirect mechanisms resulting in their proliferation, tethering and dissemination. They may represent potential targets for anticancer therapy.
It is known that following various functional mechanisms, activated platelets and the ensuing microparticles expose receptors and
Transfusion of blood components and PMPs
Many cancer patients are transfused with red blood cells, platelets or plasma in the context of their initial surgical interventions or as a supportive therapy in conjunction to chemo and radiotherapy. Transfusion may confer a poor prognosis in certain cancers [54], [55]. The presence of MPs and particularly PMPs within the transfused components [56] may affect directly and indirectly tumor growth and dissemination and increase thrombotic risks, in addition to exerting inflammatory and
Conclusions
In physiological conditions, PMPs mediate an important role in balancing health and disease, enhancing tissue repair and regeneration on one hand and hemostasis on the other [59]. In the context of cancer, however, the role of PMPs is only negative. Generated in response to tumor–platelet activation, PMPs act as coagulation promoters implicated in cancer-induced thrombosis and firing back on tumors, enhancing direct tumor growth through their load of growth factors. Furthermore, they help tumor
References (59)
Trousseau's syndrome: multiple definitions and multiple mechanisms
Blood
(2007)- et al.
Incidence of venous thrombosis in a large cohort of 66 329 cancer patients: results of a record linkage study
J Thromb Haemost
(2006) - et al.
Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer
J Thromb Haemost
(2008) - et al.
The platelet–cancer loop
Eur J Intern Med
(2013) - et al.
Platelet procoagulant activity and microvesicle formation. Its putative role in hemostasis and thrombosis
Biochim Biophys Acta
(1992) - et al.
Involvement of platelet-derived microparticles in tumor progression and thrombosis
(2014) - et al.
Repolarization of the membrane potential of blood platelets after complement damage: evidence for a Ca++-dependent exocytotic elimination of C5b-9 pores
Blood
(1986) - et al.
Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia
Blood
(1999) - et al.
Correlation between inhibition of cytoskeleton proteolysis and anti-vesiculation effect of calpeptin during A23187-induced activation of human platelets: are vesicles shed by filopod fragmentation?
Biochim Biophys Acta
(1994) - et al.
Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine
Blood Rev
(2014)
Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase
Biochim Biophys Acta
Platelet alpha-granules
Blood Rev
Cellular microparticles: what are they bad or good for?
J Thromb Haemost
Platelets effects on tumor growth
Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism
Thromb Res
Platelet microparticles: a potential predictive factor of survival in hormone-refractory prostate cancer patients treated with docetaxel-based chemotherapy
Eur Urol
Platelets and tumor cells: a new form of border control
Cancer Cell
Standardization of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies?
J Thromb Haemost
Atomic force microscopy: a novel approach to the detection of nanosized blood microparticles
J Thromb Haemost
Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop
J Thromb Haemost
Perioperative blood transfusion is associated with worse clinical outcomes in resected lung cancer
Ann Thorac Surg
A concise review on the role of microparticles/ microvesicles in blood components: are they clinically beneficial or harmful?
Transfus Apher Sci
The role of microparticles in inflammation and transfusion: a concise review
Transfus Apher Sci
Platelet microparticle: a sensitive physiological “fine tuning” balancing factor in health and disease
Transfus Apher Sci
Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial
Ann Surg
Long-term efficacy and safety of exemestane in the treatment of breast cancer
Patient Prefer Adherence
New insights into cancer-associated thrombosis
Arterioscler Thromb Vasc Biol
Coagulation activation and microparticle-associated coagulant activity in cancer patients
Thromb Haemost
Clinical relevance of microparticles from platelets and megakaryocytes
Curr Opin Hematol
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