Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

Dovizio, Melania; Ballerini, Patrizia; Fullone, Rosa; Tacconelli, Stefania; Contursi, Annalisa; Patrignani, Paola

doi:10.3390/ijms21249585

Cited by 32 publications

(18 citation statements)

References 220 publications

(165 reference statements)

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“…Platelets and coagulation play a crucial role in tumor progression and hematogenous metastasis and are therefore considered as valid pharmaceutical targets in anti-cancer therapy (Zhang et al, 2020). The important surveillance of platelet counts during chemotherapy, their role in chemoresitance, and the potential use of platelets as drug delivery systems in chemotherapy have recently been reviewed (Swier and Versteeg, 2017;Dovizio et al, 2020;Zhang et al, 2020). Therefore, we will not focus on this platelet-dependent aspect of chemotherapy, but will here focus on targeting platelets as relevant constituents of the TME.…”

Section: Perspectives For Translation Into Clinical Treatment Strategiesmentioning

confidence: 99%

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Obermann

Brockhaus

Eble

2021

Front. Cell Dev. Biol.

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Although platelets and the coagulation factors are components of the blood system, they become part of and contribute to the tumor microenvironment (TME) not only within a solid tumor mass, but also within a hematogenous micrometastasis on its way through the blood stream to the metastatic niche. The latter basically consists of blood-borne cancer cells which are in close association with platelets. At the site of the primary tumor, the blood components reach the TME via leaky blood vessels, whose permeability is increased by tumor-secreted growth factors, by incomplete angiogenic sprouts or by vasculogenic mimicry (VM) vessels. As a consequence, platelets reach the primary tumor via several cell adhesion molecules (CAMs). Moreover, clotting factor VII from the blood associates with tissue factor (TF) that is abundantly expressed on cancer cells. This extrinsic tenase complex turns on the coagulation cascade, which encompasses the activation of thrombin and conversion of soluble fibrinogen into insoluble fibrin. The presence of platelets and their release of growth factors, as well as fibrin deposition changes the TME of a solid tumor mass substantially, thereby promoting tumor progression. Disseminating cancer cells that circulate in the blood stream also recruit platelets, primarily by direct cell-cell interactions via different receptor-counterreceptor pairs and indirectly by fibrin, which bridges the two cell types via different integrin receptors. These tumor cell-platelet aggregates are hematogenous micrometastases, in which platelets and fibrin constitute a particular TME in favor of the cancer cells. Even at the distant site of settlement, the accompanying platelets help the tumor cell to attach and to grow into metastases. Understanding the close liaison of cancer cells with platelets and coagulation factors that change the TME during tumor progression and spreading will help to curb different steps of the metastatic cascade and may help to reduce tumor-induced thrombosis.

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Section: Perspectives For Translation Into Clinical Treatment Strategiesmentioning

confidence: 99%

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Obermann

Brockhaus

Eble

2021

Front. Cell Dev. Biol.

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“…Platelets can uptake circulating proteins and RNAs/microRNAs, thus acquiring a different intracellular molecular repertoire specific to the individual clinical condition. The analysis of platelet content (and of platelet-derived microvesicles), as a whole of transcript (transcriptomics) or proteins (proteomics), has the promise of being a novel tool for diagnosis and prognosis of several diseases, including cancer [ 41 ].…”

Section: Clinical Pharmacology Of Aspirin and Non-invasive Biomarkers...mentioning

confidence: 99%

Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Serrano

Patrignani

Stigliano³

et al. 2022

Genes

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Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers.

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“…Circulating platelets interact with tumour cells during their life cycle to obtain tumour-related biomolecules; additionally, they can continuously ingest and enrich circulating free proteins, nucleic acids, vesicles and particles. 86 There are two main sources of protein in the cytoplasm: one is inherited from its precursor megakaryocytes, such as platelet factor 4; the other is taken from the blood, such as P-selectin, Fibrinogen, etc. ; and some proteins have both sources at the same time, such as platelet factor V. After platelets are educated, their proteome and RNA expression profile undergo significant changes, so they are called "tumour-educated platelets".…”

Section: Teps May Facilitate Blood-based Tumour Diagnosismentioning

confidence: 99%

Platelets: The Emerging Clinical Diagnostics and Therapy Selection of Cancer Liquid Biopsies

Meng¹,

Sun²,

Yang³

et al. 2021

OTT

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Due to the inherent molecular heterogeneity of metastatic tumours and the dynamic evolution ability of tumour genomes, tumour tissues obtained through biopsy and other methods cannot capture all of the features of tumour genomes. A new diagnostic concept called "liquid biopsy" has received widespread attention in recent years. Liquid biopsy has changed the clinical practice of oncology and is widely used to guide targeted drug utilization, monitor disease progression and track drug resistance. The latest research subject in liquid biopsy is platelets. Platelets originate from multifunctional haematopoietic stem cells in the bone marrow haematopoietic system. They are small cells from the cytoplasm of bone marrow megakaryocytes. Their main physiological functions are to participate in the processes of physiological haemostasis and coagulation. Tumour cells transfer biomolecules (such as RNA) to platelets through direct contact and release of exosomes, which changes the platelet precursor RNA. Under the stimulation of tumour cells and the tumour microenvironment, platelet precursor mRNA is spliced into mature RNA and converted into functional protein to respond to external stimuli, forming tumoureducated platelets (TEPs). The detection of TEPs in the peripheral blood of patients is expected to be used in clinical tumour diagnosis. This emerging liquid biopsy method can replace and supplement the current tumour detection methods. Further research on the role of platelets in tumour diagnosis will help provide a novel theoretical basis for clinical tumour diagnosis.

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Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

Cited by 32 publications

References 220 publications

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Platelets: The Emerging Clinical Diagnostics and Therapy Selection of Cancer Liquid Biopsies

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