Role of tissue factor expression in thrombin generation by canine tumor cells

Gruber, Erika J.; Catalfamo, James L.; Stokol, Tracy

doi:10.2460/ajvr.77.4.404

Cited by 8 publications

(13 citation statements)

References 42 publications

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“…Similarly, a greater amount of TF protein was found in canine gliomas of higher histologic grades than in those of lower grades. 25 Tissue factor expression is often upregulated in meta-static tumors, compared with nonmetastatic tumors, in human patients 38,39 and is thought to be associated with metastatic potential. This could also be true for canine hemangiosarcoma, but further studies, which particularly examine TF expression in primary and metastatic hemangiosarcoma in situ, are needed.…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon was also not unique to these cell lines because we previously found similar results with other canine tumor cells in human plasma. 25 …”

Section: Discussionmentioning

confidence: 99%

“…33 The assay was performed with modifications as previously described. 25 Specifically, whereas human plasma is typically combined with an external clotting trigger (negatively charged phospholipids and recombinant human TF), no external trigger was added to test samples in the present study, and canine hemangiosarcoma cells were the source of these factors. Detached cells were washed free of culture medium with PBS and suspended at a concentration of 2 × 10 4 cells/20 μL of HEPES-buffered saline solution (10mM HEPES, c 137mM sodium chloride, f 0.5% bovine serum albumin d [wt/vol], 4mM potassium chloride, f and 10μM glucose f [pH, 7.05]) in a black 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…Functional TF expression in vitro has been identified in epithelial tumor cells and some mesenchymal tumor (including osteosarcoma and fibrosarcoma) cell lines from dogs. 24,25 Two studies 26,27 have shown that TF is expressed in canine gliomas and mammary tumors in situ. Higher TF expression was associated with higher-grade tumors, and there was evidence of coagulation activation, with intravascular thrombosis and intratumoral deposition of fibrin or fibrinogen, and fibrin or fibrinogen breakdown products, including D-dimer in the study 27 of gliomas.…”

mentioning

confidence: 99%

“…26 In an investigation in our laboratory, results of CAT revealed that TF-expressing canine mammary tumor cells generate thrombin in vitro, supporting a primary role for TF in hypercoagulability and thrombosis in dogs with mammary tumors. 25 It is not currently known whether TF is expressed and functionally procoagulant (ie, capable of generating thrombin) in dogs with hemangiosarcoma. The objective of the study reported here was to evaluate the expression of TF and generation of thrombin by canine hemangiosarcoma cells in vitro.…”

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confidence: 99%

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Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines

Witter¹,

Gruber²,

Lean³

et al. 2017

ajvr

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OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor–replete or specific coagulation factor–deficient human plasma by calibrated automated thrombography. Corn trypsin inhibitor and annexin V were used to examine contributions of contact activation and membrane-bound phosphatidylserine, respectively, to thrombin generation. RESULTS All cell lines expressed TF mRNA and antigen, with significantly greater expression of both products in SB-HSA and Emma cells than in CnAoEC. A greater percentage of SB-HSA cells expressed TF antigen, compared with other hemangiosarcoma cell lines. All hemangiosarcoma cell lines generated significantly more thrombin than did CnAoEC in canine or factor-replete human plasma. Thrombin generation induced by SB-HSA cells was significantly lower in factor VII-deficient plasma than in factor-replete plasma and was abolished in factor X–deficient plasma; residual thrombin generation in FVII-deficient plasma was abolished by incubation of cells with annexin V. Thrombin generation by SB-HSA cells was unaffected by the addition of corn trypsin inhibitor. CONCLUSIONS AND CLINICAL RELEVANCE Hemangiosarcoma cell lines expressed procoagulant TF in vitro. Further research is needed to determine whether TF can be used as a biomarker for hemostatic dysfunction in dogs with hemangiosarcoma.

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Section: Discussionmentioning

confidence: 99%

“…This phenomenon was also not unique to these cell lines because we previously found similar results with other canine tumor cells in human plasma. 25 …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines

Witter¹,

Gruber²,

Lean³

et al. 2017

ajvr

Self Cite

View full text Add to dashboard Cite

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Preoperative Thromboelastographic Profile of Patients with Congenital Heart Disease: Association of Hypercoagulability and Decreased Heparin Response

Fang

Bernier

Emani

et al. 2018

Journal of Cardiothoracic and Vascular Anesthesia

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A prospective evaluation of the prevalence of thromboemboli and associated hemostatic dysfunction in dogs with carcinoma or sarcoma

Pazzi,

Fosgate,

Rixon

et al. 2023

Veterinary Internal Medicne

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BackgroundKnowledge of the prevalence of thromboemboli and the associated hemostatic status in dogs with carcinoma or sarcoma is unknown and might allow earlier intervention.ObjectivesEstimate prevalence of thromboemboli and their association with hemostatic changes in dogs with carcinomas or sarcomas; estimate predictive values of hemostatic variables for thromboembolic disease in tumor‐bearing dogs.AnimalsThirty‐two dogs with sarcoma, 30 with carcinoma, 20 healthy age‐controlled dogs.MethodsProspective cross‐sectional study. A hemostasis panel (platelet concentration, thromboelastography, fibrinogen and D‐dimer concentration, factor X, VII and antithrombin activity) was performed in all dogs. Tumor‐bearing dogs underwent complete post mortem and histopathological evaluation. Comparisons between healthy dogs and tumor‐bearing dogs with and without intracavitary hemorrhage; and tumor‐bearing dogs with and without microthrombi were analyzed.ResultsThromboembolic disease was identified in 32/62 (52%, 95% CI: 39%‐65%) tumor‐bearing dogs. Microthrombi were identified in 31/62 (50%, 95% CI: 37%‐63%) dogs, 21/31 (68%, 95% CI: 49%‐83%) had exclusively intra‐tumoral microthrombi, 10/31 (32%, 95% CI: 17%‐51%) had distant microthrombi. Macrothrombi were identified in 3 tumor‐bearing dogs. Hemostatic changes potentially consistent with overt and non‐overt disseminated intravascular coagulation were identified in some tumor‐bearing dogs. D‐dimer concentrations were significantly higher (P = .02) and platelet concentration significantly lower (P = .03) in tumor‐bearing dogs with microthrombi compared to tumor‐bearing dogs without microthrombi. D‐dimer concentration above 500 ng/mL was 80% sensitive and 41% specific for the prediction of microthrombi presence.ConclusionThe high microthrombi prevalence and concomitant hemostatic dysfunction in dogs with carcinomas or sarcomas has not previously been reported, though the clinical importance is unknown. Increased D‐dimer concentration might increase suspicion of microthrombi.

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Role of tissue factor expression in thrombin generation by canine tumor cells

Cited by 8 publications

References 42 publications

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines

Preoperative Thromboelastographic Profile of Patients with Congenital Heart Disease: Association of Hypercoagulability and Decreased Heparin Response

A prospective evaluation of the prevalence of thromboemboli and associated hemostatic dysfunction in dogs with carcinoma or sarcoma

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