Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation.

Bromberg, Michael; Konigsberg, William H.; Madison, Jennifer; Pawashe, Aruna B.; Garen, Alan

doi:10.1073/pnas.92.18.8205

Cited by 293 publications

(271 citation statements)

References 21 publications

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“…In non-small cell lung carcinoma, the correlation was demonstrated between TF expression and angiogenic indicators exemplified by microvessel density (MVD) and VEGF expression, and co-localization of TF and VEGF was shown in both lung cancer and breast cancer cells (Koomägi and Volm, 1998;Shoji et al, 1998). TF expression in melanoma cells induced metastasis independent of the blood coagulation pathway (Bromberg et al, 1995), and, to the contrary, inhibition of TF function in human melanoma cells led to reduced haematogenous metastasis (Mueller et al, 1992). These findings suggest that TF is deeply involved in tumour progression both as an initiator of the coagulation pathway and as a mediator of signal transduction.…”

mentioning

confidence: 68%

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration

Ueno¹,

Toi²,

et al. 2000

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Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. Recently, the intracellular function of TF has been revealed to be involved in cancer invasion, independent of the blood coagulation pathway. To evaluate the clinical significance of TF expression, we performed an enzyme-linked immunosorbent assay (ELISA) in the plasma of 67 breast cancer patients and immunohistochemistry in 213 breast cancer tissues. In the ELISA study, we showed an up-regulation of plasma TF concentration in breast cancer patients compared with normal controls. Immunohistochemistry demonstrated that TF was expressed in tumour cells and stromal cells and tumour TF expression closely correlated with stromal TF expression ( P = 0.0005). The concentration of plasma TF was associated with tissue TF expression in both tumour and stroma. The multivariate analysis demonstrated that tumour TF expression was an independent prognostic indicator for overall survival ( P = 0.0452). Our data show that plasma TF concentration reflects tissue TF expression and tumour TF expression can provide some predictive value for prognosis and distant metastasis, which indicates the importance of TF function in tumour progression. © 2000 Cancer Research Campaign

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confidence: 68%

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration

Ueno¹,

Toi²,

et al. 2000

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“…3 been shown to be intrinsically procoagulant, as evidenced by correlations between the level of tissue factor (TF) expression (cell surface catalyst of local coagulation) and increased tumor growth rates. [4][5][6][7] In this manner, a cancer cell potentially uses a coagulation-dependent autocrine system by activating coagulation through thrombin, which augments the malignant phenotype.…”

Section: Introductionmentioning

confidence: 99%

Thrombin induces osteosarcoma growth, a function inhibited by low molecular weight heparin in vitro and in vivo

Ichikawa

Cole

Magnussen

et al. 2011

Cancer

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BACKGROUND: Procoagulant states, leading to activation of the coagulation protease thrombin, are common in cancer and portend a poor clinical outcome. Although procoagulant states in osteosarcoma patients have been described, studies exploring osteosarcoma cells' ability to directly contribute to procoagulant activity have not been reported. This study explores the hypothesis that osteosarcoma can regulate thrombin generation and proliferate in response to thrombin, and that attenuating thrombin generation with anticoagulants can slow tumor growth. METHODS: Pathologic analysis of osteosarcoma with adjacent venous thrombus was performed. In vitro proliferation assays, cell-based coagulant activity assays, and quantification of coagulation cofactor expression were performed on human and murine osteosarcoma cell lines with varying aggressiveness. The efficacy of low molecular weight heparin (LMWH) attenuation of tumor-dependent thrombin generation and growth in vitro and in vivo was determined. RESULTS: Venous thrombi adjacent to osteosarcoma were found to harbor tumor surrounded by fibrin expressing coagulation cofactors, a finding associated with poor clinical outcome. More aggressive osteosarcoma cell lines had greater surface expression of procoagulant factors and generated more thrombin than less aggressive cell lines and were found to proliferate in response to thrombin. Treatment with LMWH reduced in vitro osteosarcoma proliferation and procoagulant activity as well as tumor growth in vivo. CONCLUSIONS: These findings suggest that elements of the coagulation cascade may play a role in and represent a pharmaceutical target to disrupt osteosarcoma growth. They also have broader implications, as they suggest that, to be effective, dosing of anticoagulants must take into account an individual tumor's capacity to generate thrombin. Cancer 2012;118:2494

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“…Although the primary function of TF in the adult is to initiate blood coagulation (reviewed in Edgington et al, 1991), recent studies suggest that TF may contribute to blood vessel maturation in the developing embryo (Bugge et al, 1996;Carmeliet et al, 1996), to maintenance of the placental labyrinth during gestation (Erlich et al, 1999), and to tumor angiogenesis (Contrino et al, 1996). Tissue factor has also been implicated as a determinant of metastatic potential in melanoma cells (Mueller et al, 1992;Bromberg et al, 1995) and expression of TF in the stromal compartment of breast carcinomas has been shown to correlate with progression to invasive cancer (Contrino et al, 1996;Vrana et al, 1996). Thus, it is important to understand how TF gene expression is regulated in both normal and neoplastic cell types.…”

Section: Introductionmentioning

confidence: 99%

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

et al. 2000

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Serum-stimulation of quiescent mouse ®broblasts results in transcriptional activation of tissue factor (TF), the cellular initiator of blood coagulation. This requires the rapid entry of c-Fos into speci®c AP-1 DNA-binding complexes and can be strongly inhibited by the adenovirus E1A 12S gene product. In this study, we utilized a panel of E1A mutants de®cient in cellular protein binding to analyse the molecular basis for E1A inhibition of a minimal, c-Fos-dependent TF promoter/ reporter construct in mouse AKR-2B ®broblasts. Mutations which impaired binding of the retinoblastoma tumor suppressor protein family members pRB, p107, and p130 relieved E1A-mediated inhibition of transcription in response to serum-stimulation or c-Fos overexpression. Inhibition was restricted to the G 0 to G 1 transition, consistent with the speci®city of E1A for hypophosphorylated forms of RB proteins. Although E1A mutants de®cient in CBP/p300 binding retained the ability to inhibit TF transcription, deletion of the aminoterminal portion of the CBP/p300 interaction domain was required to permit rescue of TF promoter activity by coexpression of pRB. Moreover, ectopic p107 could e ectively substitute for pRB in relieving E1A-mediated repression. In primary mouse embryo ®broblasts, activity of the minimal AP-1-dependent TF promoter was suppressed in Rb 7/7 cells compared to parallel Rb +/7 and Rb +/+ transfectants. Ectopic expression of either pRB or p107 markedly enhanced TF promoter activity in Rb 7/7 ®broblasts. Collectively, these data imply that pRB and p107 can cooperate with c-Fos to activate TF gene transcription in ®broblasts and suggest a requirement for another, as yet unidenti®ed, E1A-binding protein. Oncogene (2000) 19, 3352 ± 3362.

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Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation.

Cited by 293 publications

References 21 publications

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration

Thrombin induces osteosarcoma growth, a function inhibited by low molecular weight heparin in vitro and in vivo

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

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