The prothrombotic activity of cancer cells in the circulation

Mitrugno, Annachiara; Tormoen, Garth W.; Kühn, Peter; McCarty, Owen J. T.

doi:10.1016/j.blre.2015.07.001

Cited by 85 publications

(80 citation statements)

References 114 publications

(164 reference statements)

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“…Similarly, activated platelets express phosphatidylserine, which catalyzes the production of thrombin and in turn converts fibrinogen into fibrin. Fibrin formation has been implicated in strengthening heterotypic platelet-cancer aggregates, ensuring their survival and transport to secondary sites [26]. …”

Section: Platelet-derived Soluble Factors and Receptors Promote Metasmentioning

confidence: 99%

See 1 more Smart Citation

Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer

Sylman

Mitrugno

Tormoen

et al. 2017

Converg. Sci. Phys. Oncol.

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Platelets are anucleate cells in the blood at concentrations of 150,000 to 400,000 cells/µL and play a key role in hemostasis. Several studies have suggested that platelets contribute to cancer progression and cancer-associated thrombosis. In this review, we provide an overview of the biochemical and biophysical mechanisms by which platelets interact with cancer cells and review the evidence supporting a role for platelet-enhanced metastasis of cancer, and venous thromboembolism (VTE) in patients with cancer. We discuss the potential for and limitations of platelet counts to discriminate cancer disease burden and prognosis. Lastly, we consider more advanced diagnostic approaches to improve studies on the interaction between the hemostatic system and cancer cells.

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Section: Platelet-derived Soluble Factors and Receptors Promote Metasmentioning

confidence: 99%

“…This process has been proposed to act as a positive feedback activation loop during cancer metastasis. Moreover, tumor cell-induced platelet activation may play a role in the development of cancer-associated thrombosis [26, 28]. …”

Section: Activation Of Platelets By Cancer Cellsmentioning

confidence: 99%

Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer

Sylman

Mitrugno

Tormoen

et al. 2017

Converg. Sci. Phys. Oncol.

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“…The observed CTC clusters numbered from two to several cells in clinical samples [4,7] and even up to 50 cells in animal experiments [15,16]. It has also been observed that CTC emboli can contain other cells, such as platelets, that may guard the tumor cells from immune elimination and promote their arrest at the endothelium [14,42]. …”

Section: The Dynamics Of Circulating Tumor Cell Microembolimentioning

confidence: 99%

“…The pattern of the blood flow and its shear stress, as well as the movement of other cells in the circulation system can affect CTC trajectory. Moreover, CTCs may also be exposed to collisions with red blood cells or adhesion to leukocytes, platelets, and microphages [42,51,66]. How individual CTCs and CTC emboli can withstand these intercellular interactions and persist in the fluid flow is not yet fully understood, and many questions are still unanswered.…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cells: When a Solid Tumor Meets a Fluid Microenvironment

Rejniak

2016

Advances in Experimental Medicine and Biology

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Solid tumor dissemination from the primary site to the sites of metastasis involves tumor cell transport through the blood or lymph circulation systems. Once the tumor cells enter the bloodstream, they encounter a new hostile microenvironment. The cells must withstand hemodynamic forces and overcome the effects of fluid shear. The cells are exposed to immunological signaling insults from leukocytes, to collisions with erythrocytes, and to interactions with platelets or macrophages. Finally, the cells need to attach to the blood vessel walls and extravasate to the surrounding stroma to form tumor metastases. Although only a small fraction of invasive cells is able to complete the metastatic process, most cancer-related deaths are the result of tumor metastasis. Thus, investigating the intracellular properties of circulating tumor cells and the extracellular conditions that allow the tumor cells to survive and thrive in this microenvironment is of vital interest. In this chapter, we discuss the intravascular microenvironment that the circulating tumor cells must endure. We summarize the current experimental and computational literature on tumor cells in the circulation system. We also illustrate various aspects of the intravascular transport of circulating tumor cells using a mathematical model based on immersed boundary principles.

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“…It is now well established that thrombocytosis and elevated circulating tissue factor levels are predictors of latter stage cancer along with increased incidence (4–8 fold) of venous thrombosis. A body of work demonstrates that platelets have the capability of interacting with circulating tumor cells (CTC) either directly or as a fibrin-associated network with neutrophils, and in so doing, prolonging the CTC circulatory half-life (7). Additionally, platelets have been reported to trigger Epithelial-Mesenchymal Transition (EMT) of cancer cells (8–10).…”

Section: Introductionmentioning

confidence: 99%

Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1

Lichtenberger

Fang

Bick

et al. 2017

Cancer Prevention Research

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The mechanism by which aspirin consumption is linked to significant reductions in the incidence of multiple forms of cancer and metastatic spread to distant tissues, resulting in increased cancer patient survival is not well understood. In this study, using colon cancer as an example, we provide both in vitro (cell culture) and in vivo (chemically-induced mouse model of colon cancer) evidence that this profound anti-neoplastic action may be associated with aspirin’s ability to irreversibly inhibit COX-1 mediated platelet activation, thereby blocking platelet-cancer cell interactions, which promote cancer cell number and invasive potential. This process may be driven by platelet-induced Epithelial-Mesenchymal Transition (EMT), as assessed using confocal microscopy, based upon changes in cell morphology, growth characteristics and fibronectin expression, and biochemical/molecular analysis by measuring changes in the expression of the EMT markers; vimentin, β-catenin, and SNAIL. We also provide evidence that a novel, GI-safer phosphatidylcholine (PC)-associated aspirin, PL2200 Aspirin, possesses the same or more pronounced actions vs unmodified aspirin with regard to antiplatelet effects (in vitro-reducing platelet activation as determined by measuring the release of thromboxane and VEGF release in culture medium; in vivo-inhibiting platelet number/activation and extravasation into tumor tissue) and chemoprevention (in vitro-inhibiting colonic cell growth, and invasive activity; in vivo-inhibiting colonic dysplasia, inflammation and tumor mass). These results suggest that aspirin’s chemopreventive effects may be due, in part, to the drug blocking the pro-neoplastic action of platelets; and the potential use of Aspirin-PC/PL2200 as an effective and safer chemopreventive agent for colorectal cancer and possibly other cancers.

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The prothrombotic activity of cancer cells in the circulation

Cited by 85 publications

References 114 publications

Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer

Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer

Circulating Tumor Cells: When a Solid Tumor Meets a Fluid Microenvironment

Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1

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