ArticleGenes & development2001
In vivo mechanisms by which tumors producing thrombospondin 1 bypass its inhibitory effects.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis.BMC medical genetics · 2020Pooled it
- LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF-β1 in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- High Level of Staufen1 Expression Confers Longer Recurrence Free Survival to Non-Small Cell Lung Cancer Patients by Promoting THBS1 mRNA Degradation.International journal of molecular sciences · 2021Article
- Platelet TSP-1 controls prostate cancer-induced osteoclast differentiation and bone marrow-derived cell mobilization through TGFβ-1.American journal of clinical and experimental urology · 2021Article
- Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells.Scientific reports · 2019Article
- Deciphering the complex role of thrombospondin-1 in glioblastoma development.Nature communications · 2019Article
- Human expression patterns: qualitative and quantitative analysis of thrombospondin-1 under physiological and pathological conditions.Journal of cellular and molecular medicine · 2018Review
- Thrombospondins and remodeling of the tumor microenvironment.Vessel plus · 2018Article
- Microenvironmental regulation of tumour angiogenesis.Nature reviews. Cancer · 2017Review
- Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide.Clinical & experimental metastasis · 2016Article
- Synergistic anticancer activity of valproate combined with nicotinamide enhances anti-proliferation response and apoptosis in MIAPaca2 cells.Molecular biology reports · 2014Article
- Matrikine and matricellular regulators of EGF receptor signaling on cancer cell migration and invasion.Laboratory investigation; a journal of technical methods and pathology · 2014Review
- Ossifying fibroma tumor stem cells are maintained by epigenetic regulation of a TSP1/TGF-β/SMAD3 autocrine loop.Cell stem cell · 2013Article
- The role of the tumor microenvironment in regulating angiogenesis.Cold Spring Harbor perspectives in medicine · 2012Article
- Extracellular matrix proteins modulate antimigratory and apoptotic effects of Doxorubicin.Chemotherapy research and practice · 2012Article
- Proteolytically Derived Endogenous Angioinhibitors Originating from the Extracellular Matrix.Pharmaceuticals (Basel, Switzerland) · 2011Article
- New agents targeting angiogenesis in glioblastoma.Chemotherapy research and practice · 2011Article
- Article
- c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-beta signaling in diffuse-type gastric carcinoma.Cancer science · 2009Article
- Thrombospondin and apoptosis: molecular mechanisms and use for design of complementation treatments.Current drug targets · 2008Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Thrombospondin 1 (TSP1) is a multifunctional protein able to activate TGFbeta and to inhibit angiogenesis in vivo. Although usually thought of as an inhibitor of tumor growth, TSP1 may sometimes be present at high levels during tumor progression, suggesting that tumors can eventually overcome their anti-tumor effects. Using a tet-repressible expression system, we demonstrate that murine TSP1 delayed the onset of tumor growth when produced in the tumor bed by rat fibrosarcoma tumor cells or by stromal fibroblasts coinjected with unmodified C6 glioma tumor cells. Yet upon prolonged exposure to TSP1, tumors came to grow at the same rate in the presence as in the absence of TSP1 and transplantation experiments showed that they had become insensitive to inhibition by TSP1 in both syngeneic and immune compromised hosts. Tumor resistance to TSP1 developed as a result of the in vivo outgrowth of pre-existing tumor cell variants that (1) secreted increased amounts of angiogenic factors that counterbalanced the inhibitory effect of TSP1 on neovascularization and (2) grew more efficiently in the presence of TSP1-activated TGFbeta. These results indicate that prolonged and continuous local delivery of a single multifunctional angiogenesis inhibitor like TSP1 to fast-growing tumors can lead to tumor resistance in vivo by fostering the outgrowth of subpopulations that are a by-product of the genetic instability of the tumor cells themselves.
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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.