Experimental metastasis and primary tumor growth in mice with hemophilia A

Länger, Florian; Amirkhosravi, Ali; Ingersoll, Susan B.; Walker, Jamie M.; Spath, Brigitte; Eifrig, B.; Bokemeyer, Carsten; Francis, John L.

doi:10.1111/j.1538-7836.2006.01883.x

Cited by 47 publications

(46 citation statements)

References 32 publications

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“…Tumorigenesis has been linked to several molecules essential for blood coagulation and normal platelet function. These include thrombin, tissue factor, platelet P-selectin, fibrinogen, and lysophosphatidic acid (3,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Together, these results suggest that platelets and their procoagulant activity support tumor metastasis, possibly by aiding tumor cells to lodge in the microvasculature and either extravasate to the surrounding tissue or grow as an intravascular tumor (17).…”

mentioning

confidence: 78%

Platelet glycoprotein Ibα supports experimental lung metastasis

Jain

Zuka

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

175

122

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The platelet paradigm in hemostasis and thrombosis involves an initiation step that depends on platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. The platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process and initiates the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis paradigm is emerging with significant platelet contributions in both tumorigenesis and inflammation. We have established congenic (N10) mouse colonies (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP Ib-IX contributes to experimental metastasis because a functional absence of GP Ib-IX correlates with a 15-fold reduction in the number of lung metastatic foci using B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of the ␣-subunit of GP Ib is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy.adhesion ͉ tumor ͉ hemostasis ͉ knockout ͉ melanoma C irculating blood platelets have an inherent adhesive potential long recognized as essential for hemostasis and thrombosis. Beyond the platelet paradigm for blood clotting and thrombosis, it is becoming apparent that the platelet's adhesive potential influences pathological events outside its role in hemostasis. Indeed, emerging hypotheses suggest the platelet paradigm in hemostasis and thrombosis, an accumulation of platelets and the elaboration of a fibrin matrix, may provide a mechanism for circulating tumor cells to metastasize. Experimental proof that platelets effect tumor metastasis was provided in models where an experimental lowering of circulating platelet counts reduced metastasis (1-3).Evidence suggests that carcinoma cells entering the circulation interact with both platelets and leukocytes to form tumor cell aggregates (1, 4). Data have suggested one mechanism linking the platelet to metastasis is a platelet ''cloak'' surrounding the tumor cell and protecting the tumor cell from immune surveillance (5, 6). Tumorigenesis has been linked to several molecules essential for blood coagulation and normal platelet function. These include thrombin, tissue factor, platelet P-selectin, fibrinogen, and lysophosphatidic acid (3,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Together, these results suggest that platelets and their procoagulant activity support tumor metastasis, possibly by aiding tumor cells to lodge in the microvasculature and either extravasate...

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mentioning

confidence: 78%

Platelet glycoprotein Ibα supports experimental lung metastasis

Jain

Zuka

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

175

122

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“…For instance, in mice with haemo philia A, a single dose of human factor VIII (FVIII) prior to intravenous tumour cell injection significantly increased the metastatic potential of B16F10 melanoma cells (89). Based on these observations it may be speculated that tumour cell-induced microvascular thrombosis has pathophysiological features that are similar to those of microvascular thrombosis following a circumscribed injury to the vessel wall (90):…”

Section: Mp-associated Tf In Blood-borne Metastasismentioning

confidence: 86%

“…It is tempting to hypothesize that this model represents a first mechanistic link between circulating TF-bearing MPs and haematogenous metastasis as well as a general explanation for how hypercoagulability promotes cancer dissemination. In fact, pretreatment of wild-type mice with human FVIII, which was likely to increase their plasma thrombin-generating capacity, appeared to render study animals more susceptible to lung metastasis (89). Compared to anticoagulant or anti-platelet strategies, however, far fewer studies have systematically investigated the effects of inherited or acquired hypercoagulability on tumour dissemination (91).…”

Section: Mp-associated Tf In Blood-borne Metastasismentioning

confidence: 99%

Crosstalk between cancer and haemostasis

Bokemeyer¹

2012

Hamostaseologie

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SummaryCancer is characterized by bidirectional interrelations between tumour progression, coagulation activation, and inflammation. Tissue factor (TF), the principal initiator of the coagulation protease cascade, is centrally positioned in this complex triangular network due to its pleiotropic effects in haemostasis, angiogenesis, and haematogenous metastasis. While formation of macroscopic thrombi is the correlate of cancer-associated venous thromboembolism (VTE), a major healthcare burden in clinical haematology and oncology, microvascular thrombosis appears to be critically important to blood-borne tumour cell dissemination. In this regard, expression of TF in malignant tissues as well as shedding of TFbearing microparticles into the circulation are thought to be regulated by defined genetic events relevant to pathological cancer progression, thus directly linking Trousseau’s syndrome to molecular tumourigenesis.Because pharmacological inhibition of the TF pathway in selective tumour types and patient subgroups would be in line with the modern concept of individualized, targeted anti-cancer therapy, this review will focus on the role of TF in tumour biology and cancer-associated VTE.

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“…Haemophiliac mice form less metastasis from experimental melanomas what could be explained with less formation of thrombin (Bruggemann, 2008). It seems that congenital bleeding disorders may have a protective effect against formation of metastasis on murine cells (Langer, 2006). Elderly patients with haemophilia will develop malignancies like normal elderly population; prostate, skin and gastrointestinal cancer .…”

Section: Malignancymentioning

confidence: 99%