Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis.

Mueller, Barbara M.; Reisfeld, Ralph A.; Edgington, Thomas S.; Ruf, Wolfram

doi:10.1073/pnas.89.24.11832

Cited by 357 publications

(314 citation statements)

References 39 publications

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“…Quantitative flow-cytometric analysis of tumor cell lines revealed that, like EGFR and HER2, TF can be aberrantly expressed on tumor cells. Compared with normal melanocytes, more than 1,000-fold increased TF expression has been reported on metastatic human melanoma cells (37). In the tumor models selected here, extracellular expression of TF was lower compared with EGFR and HER2.…”

Section: Discussionmentioning

confidence: 83%

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

Goeij

Satijn

Freitag

et al. 2015

Molecular Cancer Therapeutics

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Antibody-drug conjugates (ADC) are emerging as powerful cancer treatments that combine antibody-mediated tumor targeting with the potent cytotoxic activity of toxins. We recently reported the development of a novel ADC that delivers the cytotoxic payload monomethyl auristatin E (MMAE) to tumor cells expressing tissue factor (TF). By carefully selecting a TFspecific antibody that interferes with TF:FVIIa-dependent intracellular signaling, but not with the procoagulant activity of TF, an ADC was developed (TF-011-MMAE/HuMax-TF-ADC) that efficiently kills tumor cells, with an acceptable toxicology profile. To gain more insight in the efficacy of TF-directed ADC treatment, we compared the internalization characteristics and intracellular routing of TF with the EGFR and HER2. Both in absence and presence of antibody, TF demonstrated more efficient internalization, lysosomal targeting, and degradation than EGFR and HER2. By conjugating TF, EGFR, and HER2-specific antibodies with duostatin-3, a toxin that induces potent cytotoxicity upon antibody-mediated internalization but lacks the ability to induce bystander killing, we were able to compare cytotoxicity of ADCs with different tumor specificities. TF-ADC demonstrated effective killing against tumor cell lines with variable levels of target expression. In xenograft models, TF-ADC was relatively potent in reducing tumor growth compared with EGFR-and HER2-ADCs. We hypothesize that the constant turnover of TF on tumor cells makes this protein specifically suitable for an ADC approach.

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Section: Discussionmentioning

confidence: 83%

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

Goeij

Satijn

Freitag

et al. 2015

Molecular Cancer Therapeutics

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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: 64%

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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“…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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Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis.

Cited by 357 publications

References 39 publications

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

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

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

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