Expression of tissue factor in human cervical carcinoma tissue

Zhao, Xiaowen; Cheng, Chu Yong; Gou, Jinhai; Yi, Tao; Qian, Yanping; Du, Xue; Zhao, Xia

doi:10.3892/etm.2018.6723

Cited by 23 publications

(26 citation statements)

References 24 publications

(34 reference statements)

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“…TF binds FVIIa and subsequentely triggers the downstream coagulation cascade leading to thrombin generation and fibrin-rich-clot formation. As we contributed to show [21], enhanced TF expression has been observed in several tumor cell lines and several types of human cancers [14,[22][23][24][25][26][27]. If TF also triggers cellular signaling events that facilitate tumor progression [12,28,29], a determinant role of TF-associated coagulation mechanisms in supporting metastasis has been demonstrated [10,12,17,30,31].…”

Section: Introductionmentioning

confidence: 68%

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

et al. 2020

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Epithelial-mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3′-UTR-luciferase reporter vector assays implicated the 3′-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3′UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.

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Section: Introductionmentioning

confidence: 68%

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

et al. 2020

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“…TF has also been shown to play a role in the tumor growth, angiogenesis, and metastasis of cancer, 17 and is highly prevalent in cervical cancer, including squamous and adenocarcinoma histological subtypes. 18 , 19 The antibody moiety of TV is conjugated to monomethyl auristatin E (MMAE) via a valine citrulline linker, which is proteolytically cleaved and released following internalization of TV into cancer cells expressing TF. 15 , 16 MMAE is a microtubule disruptor and kills actively dividing cancer cells that have internalized TV.…”

Section: Introductionmentioning

confidence: 99%

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

et al. 2022

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New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.

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“…In oncogenesis, TF plays a role in tumor-associated angiogenesis, progression, and metastasis (20)(21)(22)(23). Tissue factor is aberrantly expressed across many solid tumors, including cervical cancer (20,(24)(25)(26), and has been associated with poor clinical outcomes (20). The expression of TF across tumor types and its role in oncogenesis make it an appealing therapeutic target.…”

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confidence: 99%

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

Hong

Concin

Vergote

et al. 2020

Clinical Cancer Research

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◥Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623).Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity.Results: Of the 55 patients, 51% had received !2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab þ doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%À37%]. Median duration of response (DOR) was 4.2 months (range: 1.0 þ À9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%À43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%À35%), median DOR of 6.0 months (range: 1.0 þ À9.7), and 6-month PFS rate of 40% (95% CI: 24%À55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed.Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.Cervical cancer is a common cancer in women, with an estimated 570,000 new cases globally in 2018, and represents the third leading cause of cancer-related death in women worldwide (1). Approximately 15,500 and 61,000 new cases of cervical cancer were estimated in North America and in Europe in 2018, respectively, resulting in approximately 5,800 and 25,800 deaths (2). Recurrent or metastatic cervical cancer has a poor prognosis, with a 5-year survival rate of 17% (3). Bevacizumab and doublet chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) were adopted as first-line (1L) standard-ofcare therapy for recurrent or metastatic cervical cancer in the past 5 years (4-6). However, nearly all patients relapse after 1L treatment, and single-institution experiences indicate that the percentage of patients who receive a second-line (2L) therapy varies (30%-70%) as many patients die before receiving treatment (7,8).Available 2Lþ therapies for recurrent or metastatic cervical cancer are characterized by low response rates (5,6). Before adoption of bevacizumab plus doublet chemotherapy in 1L, therapies administered in the 2Lþ setting reported response rates in the range of 4.5% to 15%, with median s...

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Expression of tissue factor in human cervical carcinoma tissue

Cited by 23 publications

References 24 publications

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

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