The endothelial barrier and cancer metastasis: Does the protective facet of platelet function matter?

Smęda, Marta; Przyborowski, Kamil; Stojak, Marta; Chłopicki, Stefan

doi:10.1016/j.bcp.2020.113886

Cited by 20 publications

(19 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…could be ascribed to bone marrow where recruitment of haematopoietic stem cells (HSCs) is regulated by COX [30]. Finally, given the recent discovery of the role of platelets in non-classical haemostasis, negative effects of long-term treatment with low-dose ASA could be attributed to impaired endothelial barrier constantly supported by platelets by various mechanisms particularly in the lungs [43][44][45].…”

Section: Plos Onementioning

confidence: 99%

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Long-term administration of acetylsalicylic acid (ASA) was effective in prevention of colorectal cancer, whereas the efficacy of this compound in other cancer types, including breast cancer, has been less convincingly documented. Indeed, the antimetastatic effect of lowdose ASA was observed only in the early intravascular phase of metastasis of breast cancer. In the present work, we characterized the effects of long-term treatment with ASA on the late phase of pulmonary metastasis in a mouse orthotopic 4T1 breast cancer model. Mice were treated with ASA at a dose of 12 mg�kg-1 of body weight daily starting one week prior to inoculation of 4T1 breast cancer cells, and the treatment was continued throughout progression of the disease. ASA administration decreased platelet TXB 2 production in ex vivo assays but did not change thrombin-induced platelet reactivity. Although the number of metastases in the lungs remained unchanged in ASA-treated mice, infiltration of inflammatory cells was increased concomitantly with higher G-CSF and serotonin concentrations in the lungs. Pulmonary NO production was compromised compared to control 4T1 mice. ASA treatment also evoked an increase in platelet and granulocyte counts and decreased systemic NO bioavailability along with increased markers of systemic oxidant stress such as higher GSSG/lower GSH concentrations in RBC. Analysis of eicosanoids in stirred blood demonstrated that administration of ASA at a dose of 12 mg�kg-1 to cancer-bearing mice had an effect beyond inhibition of platelet COX-1, suggesting long-term treatment with lowdose aspirin is not a selective murine platelet COX-1/TXA 2 pathway inhibitor in cancer-bearing mice. In summary, quite surprisingly, long-term treatment with low-dose ASA administered until the advanced phase of breast cancer in a murine orthotopic model of 4T1 breast cancer negatively affected the phenotype of the disease.

show abstract

Section: Plos Onementioning

confidence: 99%

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“… 8 Platelet-dependent mechanisms maintaining endothelial barrier also operate in a number of other conditions, including bacterial infections, injection of immune complexes and irritants, ischaemia–reperfusion, and irradiation, 6 and may be of importance in cancer-related inflammation, as recently reviewed by us. 9 …”

Section: Classical and Non-classical Inflammation-associated Haemostamentioning

confidence: 99%

“…( B ) Platelet-dependent mechanisms of inflammation-associated haemostasis preventing bleeding associated with inflammation are stimulus and organ dependent and may involve the platelet hemITAM receptor CLEC-2 activated by podoplanin (expressed, for example, on activated monocytes), platelet ITAM FcRc receptor functionally associated with platelet collagen receptor GPVI, platelet secretion of factors supporting the endothelial barrier (angiopoetin-1), and/or direct sealing of the hole within the endothelial monolayer by platelets. 6 , 9 , 11 , 15 …”

Section: Classical and Non-classical Inflammation-associated Haemostamentioning

confidence: 99%

“…Although they initially seemed to be quite distinct and independent from coagulation-related mechanisms, recent evidence suggests that they overlap with classical prothrombotic platelet pathways. Platelets may prevent inflammatory bleeding by (i) the release of endothelium-stabilizing factors from platelet granules; (ii) the activation of platelet C-type lectin receptor CLEC-2 containing the hemITAM motif (binding to podoplanin or S100A13) or the activation of the platelet collagen GPVI receptor associated constitutively with the FcRγ; (iii) by direct interaction of single platelets plugging the exit sites for erythrocytes within the endothelial monolayer ( Figure 1B ) 6 , 9 .…”

Section: Classical and Non-classical Inflammation-associated Haemostamentioning

confidence: 99%

See 1 more Smart Citation

Endothelial barrier integrity in COVID-19-dependent hyperinflammation: does the protective facet of platelet function matter?

Smęda

Chłopicki

2020

Cardiovascular Research

Self Cite

View full text Add to dashboard Cite

“…All in all, many different molecular associations underlie platelet-cancer cell interactions and a better insight into these pathways may provide targets for treatment of both cancer and its associated VTE risk in elderly patients. With platelets playing multiple roles in cancer progression, care needs to be taken when using platelet inhibitors [189].…”

Section: Platelets Drive Tumor Growth Angiogenesis and Metastasis Imentioning

confidence: 99%

Platelets in aging and cancer—“double-edged sword”

Faria

Andrade²,

Peppelenbosch

et al. 2020

Cancer Metastasis Rev

View full text Add to dashboard Cite

Platelets control hemostasis and play a key role in inflammation and immunity. However, platelet function may change during aging, and a role for these versatile cells in many age-related pathological processes is emerging. In addition to a well-known role in cardiovascular disease, platelet activity is now thought to contribute to cancer cell metastasis and tumor-associated venous thromboembolism (VTE) development. Worldwide, the great majority of all patients with cardiovascular disease and some with cancer receive anti-platelet therapy to reduce the risk of thrombosis. However, not only do thrombotic diseases remain a leading cause of morbidity and mortality, cancer, especially metastasis, is still the second cause of death worldwide. Understanding how platelets change during aging and how they may contribute to aging-related diseases such as cancer may contribute to steps taken along the road towards a "healthy aging" strategy. Here, we review the changes that occur in platelets during aging, and investigate how these versatile blood components contribute to cancer progression.

show abstract

The endothelial barrier and cancer metastasis: Does the protective facet of platelet function matter?

Cited by 20 publications

References 118 publications

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Endothelial barrier integrity in COVID-19-dependent hyperinflammation: does the protective facet of platelet function matter?

Platelets in aging and cancer—“double-edged sword”

Contact Info

Product

Resources

About