Platelet Activation Induced by a Human Neuroblastoma Tumor Cell Line Is Reduced by Prior Administration of Ticlopidine

Bastida, E; Escolar, Ginés; Almirall, L; Ordinas, Antonio

doi:10.1055/s-0038-1661558

Cited by 35 publications

(29 citation statements)

References 8 publications

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“…TXA2 (34) and ADP (35,36) are considered to be ‘soluble stimulators’ of platelet aggregation. In this study, we observed that the TXA2 and ADP pathways are activated during MCF-7 cell-induced TCIPA.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Lian

et al. 2012

Oncology Letters

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Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets. Tumor cell-induced platelet aggregation (TCIPA) contributes significantly to hematogenous metastasis; however, the molecular mechanisms involved in breast cancer TCIPA are poorly characterized. In this study, MCF-7 metastatic human breast cancer cells induced dose-dependent aggregation of washed platelets. Four major platelet activation pathways, glycoprotein (GP)-Ib-IX, GPIIb/IIIa, thromboxane (TX)-A2 and adenosine diphosphate (ADP) were activated during TCIPA and were inhibited by their respective inhibitors, 7E3, SZ-1, aspirin and apyrase. Pretreatment of platelets with 7E3, SZ-1 or apyrase significantly inhibited TCIPA, while pretreatment with aspirin had no effect. Moreover, combined pretreatment of platelets with 7E3, SZ-1 and apyrase significantly inhibited TCIPA, compared to single inhibitors. Combinations of antiplatelet drugs may represent a promising strategy to prevent cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Lian

et al. 2012

Oncology Letters

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“…Using several different cell lines it has been demonstrated that various human and animal tumor cells have the ability to aggregate platelets and that this capacity correlates with the tumor's metastatic potential. [8][9][10][11][12][13][14][15] In addition, platelet activation has been established in several malignancies. 6 Further support of the interaction between platelets and tumor cells is the recent advancements demonstrating antiplatelet agents can impact malignancy.…”

Section: Introductionmentioning

confidence: 99%

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Battinelli

Markens

Italiano

2011

Blood

328

290

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“…16,17 Tumor cells can aggregate platelets, and this ability correlates with the tumor's metastatic potential. [18][19][20][21][22] The association between hemostasis and malignancy was first recognized by Armand Trousseau in 1865. 23 This relationship is strengthened by the observation that treatment with anticoagulants can improve survival.…”

Section: Introductionmentioning

confidence: 99%

Anticoagulation inhibits tumor cell–mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response

Battinelli

Markens

Kulenthirarajan

et al. 2014

Blood

102

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• Anticoagulants inhibit release of angiogenic proteins from platelets.Platelets are a reservoir for angiogenic proteins that are secreted in a differentially regulated process. Because of the propensity for clotting, patients with malignancy are often anticoagulated with heparin products, which paradoxically offer a survival benefit by an unknown mechanism. We hypothesized that antithrombotic agents alter the release of angiogenesis regulatory proteins from platelets. Our data revealed that platelets exposed to heparins released significantly decreased vascular endothelial growth factor (VEGF) in response to adenosine 59-diphosphate or tumor cells (MCF-7 cells) and exhibited a decreased angiogenic potential. The releasate from these platelets contained decreased proangiogenic proteins. The novel anticoagulant fondaparinux (Xa inhibitor) demonstrated a similar impact on the platelet angiogenic potential. Because these anticoagulants decrease thrombin generation, we hypothesized that they disrupt signaling through the platelet protease-activated receptor 1 (PAR1) receptor. Addition of PAR1 antagonists to platelets decreased VEGF release and angiogenic potential. Exposure to a PAR1 agonist in the presence of anticoagulants rescued the angiogenic potential. In vivo studies demonstrated that platelets from anticoagulated patients had decreased VEGF release and angiogenic potential. Our data suggest that the mechanism by which antithrombotic agents increase survival and decrease metastasis in cancer patients is through attenuation of platelet angiogenic potential. (Blood. 2014;123(1):101-112) IntroductionCancer cells are surrounded by and interact with a complex milieu consisting of but not limited to endothelial cells, mast cells, macrophages, stromal cells, and lymphocytes. In fact, tumor cells live in intimate symbiosis with the rest of the body and appear to hijack normal physiological processes to aid their progression and growth. The recognition that tumor growth and metastasis is not exclusively an independent process for tumor cells suggests that disrupting the tumor microenvironment might provide a novel treatment modality for malignancy.Although platelets are best known for their role in hemostasis and thrombosis, a substantial amount of data supports the idea that platelets play important roles in tumorigenesis, contributing to inflammation, angiogenesis, and metastatic dissemination of tumor cells.1 Platelet count can be a prognostic factor in cancer, patients presenting with thrombocytosis having a poor survival in a variety of cancers including breast cancer.2-5 Conversely, the presence of thrombocytopenia is associated with a survival benefit and decreased metastasis.6-9 For tumors to grow beyond 1 to 2 mm 3 , they must establish their own blood supply through angiogenesis, and there is substantial evidence that angiogenesis is regulated by platelets. [10][11][12] In malignancy, platelets are the major serum source of many potent proangiogenic proteins, including more than 80% of circulating vascul...

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Platelet Activation Induced by a Human Neuroblastoma Tumor Cell Line Is Reduced by Prior Administration of Ticlopidine

Cited by 35 publications

References 8 publications

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Anticoagulation inhibits tumor cell–mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response

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