Platelets: “First Responders” in Cancer Progression and Metastasis

Menter, David G.; Davis, Jennifer S.; Tucker, Stephanie C.; Hawk, Ernest T.; Crissman, John D.; Sood, Anil K.; Kopetz, Scott; Honn, Kenneth V.

doi:10.1007/978-3-319-47462-5_74

Cited by 5 publications

(11 citation statements)

References 244 publications

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“…“First Responders” describes platelets as active participants in the hemostasis, wounding, immune, and metastatic processes [1,2]. Platelets often remain unheeded during in vivo experimental studies or pathologic observations.…”

Section: Platelet “First Responder” Propertiesmentioning

confidence: 99%

“…These first responder interactions are driven by a variety of platelet glycoprotein receptors that can fail in many congenital platelet disorders [32,2]. These receptors can bind extracellular matrix factors that include proteoglycans, laminin, fibronectin, and vitronectin along with various isoforms of collagen.…”

Section: Platelet “First Response” Facilitated Clot/wound Biologymentioning

confidence: 99%

“…The first responder role to threats is thought to be the reason why platelets evolved to have both haemostatic and immune properties [174,2,175,176,163]. This is best highlighted in the wound response model whereby platelets have a unique role in recognizing tissue damage and stimulating more specialized immune cells to infiltrate and initiate the sterilization of the area, particularly where a pathogen may have been introduced past physical barriers.…”

Section: Platelet Mediated Thrombogenesis Inflammatory and Resolutimentioning

confidence: 99%

Section: Platelet “First Response” Facilitated Cancer Progressionmentioning

confidence: 99%

“…As a part of the metastatic process, platelet receptors recognize complexes of tumor cell receptors surface bound matrix proteins or cellular products as they invade blood vessels due to platelet-tumor cell first response interactions [130,2,190]. Extensive membrane changes occur at bilayer interfaces between platelets and tumor cells [2,1,191,192]. Tumor cells form extensive membrane/cytoskeletal processes that heavily interdigitate with a central platelet aggregate and involves the uptake of platelet fragments and mitochondria [2,1,191,192].…”

Section: Platelet “First Response” Facilitated Cancer Progressionmentioning

confidence: 99%

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Platelet “first responders” in wound response, cancer, and metastasis

Menter

Kopetz

Hawk

et al. 2017

Cancer Metastasis Rev

Self Cite

146

115

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Platelets serve as “First Responders” during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities. Functionally, platelets normally initiate rapid clotting, vasoconstriction, inflammation and wound biology that leads to sterilization, tissue repair and resolution. Platelets also are among the first to sense, phagocytize, decorate, or react to pathogens in the circulation. These platelet first responder properties are commandeered during chronic inflammation, cancer progression and metastasis. Leaky or inflammatory reaction blood vessel genesis during carcinogenesis provides opportunities for platelet invasion into tumors. Cancer is thought of as a non-healing or chronic wound that can be actively aided by platelet mitogenic properties to stimulate tumor growth. This growth ultimately outstrips circulatory support leads to angiogenesis and intravasation of tumor cells into the blood stream. Circulating tumor cells reengage additional platelets, which facilitates tumor cell adhesion, arrest and extravasation and metastasis. This process, along with the hypercoagulable states associated with malignancy is amplified by IL6 production in tumors that stimulate liver thrombopoietin production and elevates circulating platelet numbers by thrombopoiesis in the bone marrow. These complex interactions and the “First Responder” role of platelets during diverse physiologic stresses provides a useful therapeutic target that deserves further exploration.

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Section: Platelet “First Responder” Propertiesmentioning

confidence: 99%

Section: Platelet “First Response” Facilitated Clot/wound Biologymentioning

confidence: 99%

Section: Platelet Mediated Thrombogenesis Inflammatory and Resolutimentioning

confidence: 99%

Section: Platelet “First Response” Facilitated Cancer Progressionmentioning

confidence: 99%

Section: Platelet “First Response” Facilitated Cancer Progressionmentioning

confidence: 99%

See 3 more Smart Citations

Platelet “first responders” in wound response, cancer, and metastasis

Menter

Kopetz

Hawk

et al. 2017

Cancer Metastasis Rev

Self Cite

146

115

View full text Add to dashboard Cite

show abstract

Silica nanoparticles enhance the cyto- and hemocompatibility of a multilayered extracellular matrix scaffold for vascular tissue regeneration

Goldberg,

Zomer,

McFetridge

et al. 2024

Biotechnol Lett

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Platelet-targeted pharmacologic treatments as anti-cancer therapy

Gresele

Momi

Malvestiti

et al. 2017

Cancer Metastasis Rev

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Platelets act as multifunctional cells participating in immune response, inflammation, allergy, tissue regeneration, and lymphoangiogenesis. Among the best-established aspects of a role of platelets in non-hemostatic or thrombotic disorders, there is their participation in cancer invasion and metastasis. The interaction of many different cancer cells with platelets leads to platelet activation, and on the other hand platelet activation is strongly instrumental to the pro-carcinogenic and pro-metastatic activities of platelets. It is thus obvious that over the last years a lot of interest has focused on the possible chemopreventive effect of platelet-targeted pharmacologic treatments. This article gives an overview of the platelet-targeted pharmacologic approaches that have been attempted in the prevention of cancer development, progression, and metastasis, including the application of anti-platelet drugs currently used for cardiovascular disease and of new and novel pharmacologic strategies. Despite the fact that very promising results have been obtained with some of these approaches in pre-clinical models, with the exclusion of aspirin, clinical evidence of a beneficial effect of anti-platelet agents in cancer is however still largely missing. Future studies with platelet-targeted drugs in cancer must carefully deal with design issues, and in particular with the careful selection of patients, and/or explore novel platelet targets in order to provide a solution to the critical issue of the risk/benefit profile of long-term anti-platelet therapy in the prevention of cancer progression and dissemination.

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Platelets: “First Responders” in Cancer Progression and Metastasis

Cited by 5 publications

References 244 publications

Platelet “first responders” in wound response, cancer, and metastasis

Platelet “first responders” in wound response, cancer, and metastasis

Silica nanoparticles enhance the cyto- and hemocompatibility of a multilayered extracellular matrix scaffold for vascular tissue regeneration

Platelet-targeted pharmacologic treatments as anti-cancer therapy

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