Tumour-expressed tissue factor inhibits cellular cytotoxicity

Li, Chao; Colman, Lucy; Collier, Mary E.W.; Dyer, Charlotte E.; Greenman, John; Ettelaie, Camille

doi:10.1007/s00262-006-0130-1

Cited by 12 publications

(7 citation statements)

References 41 publications

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“…Sets of cells (10 6 ) were incubated with a range of lmWh concentrations (0-2,000 µg/ml) for 24 h. the cells were lysed in the presence of a protease inhibitor cocktail (active motif, rixensart, Belgium), and 20 µg of the samples was analysed using a TF-antigen ELISA kit (Affinity Biologicals, Ancaster, Canada) as previously described (14). the tF concentrations were determined against a standard curve prepared simultaneously using recombinant tF (0-200 ng/ml) (american diagnostica Inc., Stamford, USA).…”

Section: Methodsmentioning

confidence: 99%

Low molecular weight heparin suppresses tissue factor-mediated cancer cell invasion and migration in vitro

Ettelaie¹,

Fountain²,

Collier³

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Elevated expression of tissue factor (tF) has been associated with an increased risk of thrombosis in the majority of cancers. moreover, treatment of cancer patients with low molecular weight heparin (lmWh) appears to have beneficial effects that reach beyond controlling the immediate hypercoagulable state. in this study, we investigated the influence of the treatment of cancer cells with LMWH (0-2,000 µg/ml) on cell invasiveness and migration in cancer cell lines from five separate tissues; pancreatic, breast, colocarcinoma, ovarian and melanoma. the rate of cell invasion across collagen iV-coated membranes was suppressed in all cell lines tested on incubation with 2,000 µg/ml lmWh, but Bxpc-3 and mda-mB-231 cells also responded to the lowest concentration of 20 µg/ml lmWh. Furthermore, the rate of cell migration was reduced to varying extents in all of the cell lines tested on incubation with 20 µg/ml or higher concentrations of lmWh. the decrease in the rates of invasion and migration also strongly correlated with the reduction in tF protein expression and tF activity in these cells following incubation with lmWh. moreover, the lmWh-mediated decreases in cellular invasion in the most affected cell lines (Bxpc-3 and mda-mB-231) were restored by transfection of the cells with the mammalian pcmV-xl5-tF expression vector allowing independent overexpression of tF. in conclusion, lmWh appears to suppress the rate of cancer cell invasion and migration in vitro, through a mechanism that is at least in part dependent on the tF protein expression and activity in cancer cells. Introductionthe association between increased tissue factor (tF) expression and aggressiveness of cancer is well established. the expression of tF has been correlated with the histological grade of tumours (1), and the up-regulation of tF expression in cancer cells occurs early during the disease (2). Furthermore, the ability of tF to induce cellular cancer cell proliferation, migration and invasion has been documented (3-7). heparin treatment of cancer patients has been used as a means of controlling the risk of thrombotic episodes (8), and low molecular weight heparin (lmWh) has been reported to be suitable for the regulation of the procoagulant action of tF (9). there is data that incubation of cancer cell lines with lmWh results in the suppression of tF expression. additionally, we previously reported a reduction in the levels of circulating tF in the plasma from pancreatic cancer patients receiving prophylactic lmWh (daltaparin), compared to those not receiving the treatment (10). in this study, we further demonstrated the ability of lmWh to reduce the level of tF antigen and activity in cell lines from five separate tissues; BxPC-3 (pancreatic cancer), mda-mB-231 (breast cancer), loVo (colorectal cancer), SKOV-3 (ovarian cancer) and a375 (melanoma). crucially, we report that the incubation of these cancer cell lines with lmWh (20-2,000 µg/ml) reduces cellular invasion and migration through a tF-mediated mechanism in vitro. Material...

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Section: Methodsmentioning

confidence: 99%

Low molecular weight heparin suppresses tissue factor-mediated cancer cell invasion and migration in vitro

Ettelaie¹,

Fountain²,

Collier³

et al. 2011

Experimental and Therapeutic Medicine

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“…TF antigen and activity levels were measured using a TF-ELISA kit (Affinity Biologicals) and 2-stage chromogenic assay, respectively. 24,25 For details, please see supplemental material.…”

Section: Microparticle Preparationmentioning

confidence: 99%

Induction of Endothelial Cell Proliferation by Recombinant and Microparticle-Tissue Factor Involves β1-Integrin and Extracellular Signal Regulated Kinase Activation

Collier

Ettelaie

2010

ATVB

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Objective-Increased levels of circulating tissue factor (TF) in the form of microparticles increase the risk of thrombosis.However, any direct influence of microparticle-associated TF on vascular endothelial cell proliferation is not known. In this study, the influence of recombinant and microparticle-associated TF on endothelial cell proliferation and mitogen-activated protein kinase signaling mechanisms was examined. Methods and Results-Incubation

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“…The presence of surface TF antigen on breast cancer cells (5 Â 10 5 ) was examined by flow cytometry using a mouse monoclonal anti-human TF FITC-conjugated antibody (American Diagnostica) as described previously (20). TF activity on the cell surface was measured using the prothrombin time assay using cell suspensions (10 6 cells in 100 AL PBS) as described previously (11).…”

Section: Cell Culturementioning

confidence: 99%

“…The pellet was washed with PBS (1.5 mL), centrifuged as above, and resuspended in PBS (1 mL). The presence of TF antigen was examined by flow cytometry (20) and TF activity of the samples was measured using the one-stage prothrombin time assay. MCF-7 cells (2 Â 10 5 ) in 12-well plates were adapted to serum-free medium and incubated with the cell-derived microparticles (TF concentration = 47 F 5 pg/mL as determined by ELISA; ref.…”

Section: Isolation Of Cell-derived Microparticlesmentioning

confidence: 99%

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Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

Collier

Ettelaie

2008

Molecular Cancer Research

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Increased expression of tissue factor (TF) has been associated with invasive forms of breast cancer. Conversely, the loss of estrogen receptor A (ERA) is associated with increased cell invasiveness. We have examined the influence of exogenous truncated recombinant TF (rTF) on ERA expression and cell invasiveness and investigated the mechanism of rTF signaling. The influence of rTF on ERA expression in MCF-7 and T47D cell lines was investigated using reverse transcription-PCR and ELISA. Cell invasion was measured using Boyden chamber-based invasion assays. Additionally, the interaction of fluorescein-labeled rTF with the surface of MCF-7 cells and particularly with B 1 -integrin was examined. Treatment of cells with rTF resulted in the downregulation of ERA mRNA and protein over 24 h, which required B 1 -integrin and involved the mitogen-activated protein kinase pathway but did not require PAR2 activation. The addition of rTF reduced estradiol-mediated cell proliferation as well as increased cell invasiveness requiring both PAR2 and B 1 -integrin activation. Fluorescein-labeled rTF was shown to bind to the surface of MCF-7 cells within 5 min and peaked at 15 min. The bound rTF colocalized with cellular B 1 -integrin and was disrupted in the presence of excess unlabeled rTF and an anti-B 1 polyclonal antibody. Finally, affinity purification of B 1 -integrin using rTF-conjugated agarose showed a requirement for the presence of divalent cations but not factor VIIa. The results indicate that rTF is capable of down-regulating ERA expression in breast cancer cells, resulting in decreases in estrogen-mediated cell proliferation and increased invasiveness. Furthermore, the mechanisms by which rTF induces these changes involve both PAR2 and B 1 -integrin.

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Tumour-expressed tissue factor inhibits cellular cytotoxicity

Abstract: We conclude that TF can promote immune evasion in tumour cells expressing this protein leading to increased survival and therefore metastatic rate in such cells.

Cited by 12 publications

References 41 publications

Low molecular weight heparin suppresses tissue factor-mediated cancer cell invasion and migration in vitro

Low molecular weight heparin suppresses tissue factor-mediated cancer cell invasion and migration in vitro

Induction of Endothelial Cell Proliferation by Recombinant and Microparticle-Tissue Factor Involves β1-Integrin and Extracellular Signal Regulated Kinase Activation

Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

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