Platelets & Metastasis

New French review paper below [1].

I'm glad to see it, since it bolsters my view that metastasis largely depends on coagulation factors & microclots.  Coagulation & clotting are not specifically mentioned, so I'll recap the clotting process:

i)  activation of platelets (this is mentioned)

ii) aggregation of platelets to form a plug.  Fibrinogen connects the platelets.

iii) the enzyme thrombin converts fibrinogen to fibrin.  Fibrin not only provides the glue for the platelet plug, but also forms the body of the clot that builds around the plug.

According to the paper:

"It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells."

"Due to a plethora of factors released upon activation, platelet functions are ... connected to tumor growth ..."

Ideally, a newly diagnosed cancer patient would be placed on an anticoagulation drug as a metastasis inhibitor.  However, there are no such protocols.  The most common anticoagulant, Warfarin (Coumadin) is too dangerous to be used as a prophylactic.  It is one of the top drugs responsible for ER visits.

Nattokinase is an otc enzyme that mimics plasmin & degrades fibrin - i.e. dissolves clots.  But it also inhibits platelet aggregation [2].

I have written elsewhere about the use of nattokinase, & the importance of monitoring/controling coagulation factors.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/271...

Blood. 2016 May 6. pii: blood-2016-01-636399. [Epub ahead of print]

Metastasis: new functional implications of platelets and megakaryocytes.

Leblanc R1, Peyruchaud O2.

Author information

1INSERM U1068, Institut Paoli-Calmettes and Universite Aix-Marseille, Marseille, France;

2Faculte de Medecine Lyon Est, INSERM, UMR1033, UCB Lyon 1, Lyon, France olivier.peyruchaud@inserm.fr.

Abstract

Platelets are essential components of hemostasis. Due to a plethora of factors released upon activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review we describe recent insights into the molecular mechanisms supporting the pro-metastatic activity of platelets. Platelets have been shown to promote survival of circulating tumor cells (CTCs) in the bloodstream by conferring resistance to the shear stress and attack from natural killer cells. Recently, platelets were found to promote and/or maintain the state of epithelial to mesenchymal transition on CTCs through platelet secretion of transforming growth factor β in response to CTC activation. At a later stage in the metastatic process, platelets promote extravasation and establishment of metastatic cells in distant organs as observed in bone. This particular environment is also the site of hematopoiesis, megakaryocytopoiesis and platelet production. Increasing the number of megakaryocytes (MKs) in the bone marrow results in a high bone mass phenotype and inhibits skeletal metastasis formation of prostate cancer cells. As a result of their specific location in vascular niches in the bone marrow, MK activity might contribute to the "seed and soil" suitability between CTCs and bone. In conclusion, recent findings have made a great advance in our knowledge on how platelets contribute to the metastatic dissemination of cancer cells and which may support the development of new anti-metastasis therapies.

Copyright © 2016 American Society of Hematology.

PMID: 27154188 [PubMed - as supplied by publisher]

[2] ncbi.nlm.nih.gov/pmc/articl...

4 Replies

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  • However, when cancer invades the bone marrow, as in our case, healthy cells are crowded out by cancer cells and can cause severe enough thrombocytopenia that a person can experience uncontrolled bleeding.  We experienced this as well.  Patients that's develop thrombocytopenia from cancer also have a poor outcome.

    Article below is one study on non-hematologic cancers and bone marrow invasion....

    download.springer.com/stati...*~hmac=8417c0f59d01791ca71dd4cd8bebc8711fb7f1108f927c39909aeae686c91980

  • But thrombocytopenia (deficiency of platelets in the blood) is rare in PCa, & very much an end-stage event.

    -Patrick

  • There is no scientific proof for any of this?

  • Hi Fude,

    I could cite just one paper [1] since it mentions:

    a)  "Inhibition of coagulation greatly limits cancer metastasis in many experimental models."

    b)  "recent studies in which treatment of clinical cohorts with anticoagulant drugs led to diminished metastasis"

    Searching PubMed for recent <prostate anticoagulants metastasis> studies:

    [2]  "AC {anticoagulant} therapy was associated with an improvement in biochemical control in patients with prostate cancer who received RT with curative intent."  "The distant metastasis rate at 4 years ... was reduced in the AC group compared with the non-AC group (1% vs 5% ...)"

    "The association between cancer and the coagulation system is widely recognized. Cancer patients develop thromboembolism more frequently than noncancer patients, and patients who are diagnosed with idiopathic venous thrombosis are at increased risk of subsequently developing cancer. There are substantial experimental data to suggest that the coagulation system may modulate multiple cancer pathways, such as tumor proliferation, angiogenesis, host immunologic defense, and metastasis."

    [3]  "Anticoagulant use ({low-molecular-weight heparin} in particular) is an independent predictor of improved survival in men with mCRPC receiving docetaxel."

    [4]  "High-risk prostate cancer (PC) has poor outcomes due to therapeutic resistance to conventional treatments, which include prostatectomy, radiation, and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in PC patients. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit when administered with radiotherapy in patients with high-risk PC."

    "For patients taking any AC compared with no AC, there was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF was 84% vs. 65%... Aspirin use was also associated with reduced rates of distant metastases at 5 years (12.2% vs. 26.7% ...)." 

    "On subset analysis of patients with Gleason score (GS) 9–10 histology, aspirin resulted in improved 5-year OS (88% vs. 37% ...)"

    -Patrick

    [1] ncbi.nlm.nih.gov/pubmed/236...

    Br J Haematol. 2013 Aug;162(4):433-41. doi: 10.1111/bjh.12381. Epub 2013 May 21.

    Coagulation and metastasis: what does the experimental literature tell us?

    Gil-Bernabé AM1, Lucotti S, Muschel RJ.

    Author information

    1Department of Oncology, Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK.

    Abstract

    Inhibition of coagulation greatly limits cancer metastasis in many experimental models. Cancer cells trigger coagulation, through expression of tissue factor or P-selectin ligands that have correlated with worse prognosis in human clinical studies. Cancer cells also affect coagulation through expression of thrombin and release of microparticles that augment coagulation. In the cancer-bearing host, coagulation facilitates tumour progression through release of platelet granule contents, inhibition of Natural Killer cells and recruitment of macrophages. We are revisiting this literature in the light of recent studies in which treatment of clinical cohorts with anticoagulant drugs led to diminished metastasis.

    © 2013 John Wiley & Sons Ltd.

    KEYWORDS:

    aspirin; coagulation; macrophages; metastasis; tissue factor

    PMID: 23691951 [PubMed - indexed for MEDLINE]

    [2] onlinelibrary.wiley.com/doi...

    [3] ncbi.nlm.nih.gov/pmc/articl...

    [4] ncbi.nlm.nih.gov/pmc/articl...

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