ArticleThe Journal of clinical investigation2002
Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01015625 (Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer, a Multicenter Prospective Randomized Study to Evaluate the Use of Local Therapy), which is not on this map. Cited by 160 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer, a Multicenter Prospective Randomized Study to Evaluate the Use of Local Therapy
Who cites it
160 citing papers in PubMed, 371 citations in OpenAlex.
- Innovative combinatory approaches with dendritic cell-based vaccines: bridging preclinical insights and clinical challenges.Clinical and experimental medicine · 2026Review
- A preserved TGFβ cytostatic response through DLD-mediated metabolic modulation undermines anti-TGFβ therapy in gastric cancer.Nature communications · 2025Article
- Engineering DNA Origami Captors for TGFβ1 Sequestration to Enhance Tumor Immune Modulation and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TGF-Beta Induces Activin A Production in Dermal Fibroblasts Derived from Patients with Fibrodysplasia Ossificans Progressiva.International journal of molecular sciences · 2023Article
- Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.Signal transduction and targeted therapy · 2022Review
- Review
- Atovaquone Suppresses Triple-Negative Breast Tumor Growth by Reducing Immune-Suppressive Cells.International journal of molecular sciences · 2021Article
- The liver metastatic niche: modelling the extracellular matrix in metastasis.Disease models & mechanisms · 2021Review
- Homeless Cells Escape Death and Deliver Lethal Cancer.Endocrinology · 2021Article
- A Positive Feedback Loop Between TGFβ and Androgen Receptor Supports Triple-negative Breast Cancer Anoikis Resistance.Endocrinology · 2021Article
- TGFβ biology in cancer progression and immunotherapy.Nature reviews. Clinical oncology · 2021Review
- TGF-β signaling in liver metastasis.Clinical and translational medicine · 2020Review
- Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma.Scientific reports · 2020Observational
- Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-β-Induced EMT and Cancer Metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- LyP-1-Modified Oncolytic Adenoviruses Targeting Transforming Growth Factor β Inhibit Tumor Growth and Metastases and Augment Immune Checkpoint Inhibitor Therapy in Breast Cancer Mouse Models.Human gene therapy · 2020Article
- The Outcome of TGFβ Antagonism in Metastatic Breast Cancer ModelsClinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- On-Target Anti-TGF-β Therapies Are Not Succeeding in Clinical Cancer Treatments: What Are Remaining Challenges?Frontiers in cell and developmental biology · 2020Review
- Role of the tumor microenvironment in pancreatic cancer.Annals of gastroenterological surgery · 2019Review
- Long non-coding RNA SNHG20 promotes nasopharyngeal carcinoma cell migration and invasion by upregulating TGF-β1.Experimental and therapeutic medicine · 2018Article
- Cancer Associated Fibroblasts: Naughty Neighbors That Drive Ovarian Cancer Progression.Cancers · 2018Review
100 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.