ArticleBreast cancer research and treatment2011
CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo.
Article in Breast cancer research and treatment, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 86 citations in OpenAlex.
- Article
- The emerging role of microbiota in lung cancer: a new perspective on lung cancer development and treatment.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Ubiquitination-Dependent LLGL2 Degradation Drives Colorectal Cancer Progression via THBS3 mRNA Stabilization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Blocking the TCA Cycle in Cancer Cells Potentiates CD36+ T-cell-Mediated Antitumor Immunity by Suppressing ER Stress-Associated THBS2 Signaling.Cancer research · 2025Article
- Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.International journal of experimental pathology · 2024Review
- Profiling the heterogeneity of colorectal cancer consensus molecular subtypes using spatial transcriptomics.NPJ precision oncology · 2024Article
- Assessment of αClinical and experimental medicine · 2023Article
- Intratumor microbiota: a novel tumor component.Journal of cancer research and clinical oncology · 2023Review
- Clinical phenotyping of plasma thrombospondin-2 reveals relationship to right ventricular structure and function in pulmonary hypertension.ERJ open research · 2023Article
- CD36 and Its Role in Regulating the Tumor Microenvironment.Current oncology (Toronto, Ont.) · 2022Review
- Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity.The Journal of clinical investigation · 2022Article
- Biodistribution studies for cell therapy products: Current status and issues.Regenerative therapy · 2021Review
- Review
- Systematic prediction of key genes for ovarian cancer by co-expression network analysis.Journal of cellular and molecular medicine · 2020Article
- Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- Airway Microbiota as a Modulator of Lung Cancer.International journal of molecular sciences · 2020Review
- THBS2, a microRNA-744-5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors.Oncology letters · 2020Article
- CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis.Nature communications · 2019Article
- Thrombospondin 1 Triggers Osteosarcoma Cell Metastasis and Tumor Angiogenesis.Oncology research · 2019Article
- Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2.
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