ArticleBMC cancer2017
Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 271 citations in OpenAlex.
- Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis.Journal of translational medicine · 2019Pooled it
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- Amentoflavone Suppresses Stemness of Retinoblastoma Cell via Targeting Smoothened (SMO) Protein.Stem cells international · 2026Article
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- Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis.Cancer cell international · 2025Review
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- Matrix Metallopeptidase 9 Promotes Contraction in Human Uterine Myometrium.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Lung cancer: Animal model of lung cancer, molecular carcinogenesis of lung cancer, and antitumor effect ofOpen veterinary journal · 2025Review
- Licochalcone A suppresses pancreatic ductal adenocarcinoma progression by targeting eEF2K-mediated pyroptosis.Frontiers in pharmacology · 2025Article
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- Mechanism of GPR173-Mediated Suppression of TNBC Proliferation and Metastatic Potential via GnRHR Upregulation.Clinical Medicine Insights. Oncology · 2025Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRetinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis. Two such targets are matrix metalloproteinases-2 and -9 (MMP-2, -9), which degrade extracellular matrix as a prerequisite for cellular invasion and have been shown to be involved in other types of cancer metastasis. Cancer Clinical Trials with an anti-MMP-9 therapeutic antibody were recently initiated, prompting us to investigate the role of MMP-2, -9 in Rb metastasis.
methodsWe compare MMP-2, -9 activity in two well-studied Rb cell lines: Y79, which exhibits high metastatic potential and Weri-1, which has low metastatic potential. The effects of inhibitors of MMP-2 (ARP100) and MMP-9 (AG-L-66085) on migration, angiogenesis, and production of immunomodulatory cytokines were determined in both cell lines using qPCR, and ELISA. Cellular migration and potential for invasion were evaluated by the classic wound-healing assay and a Boyden Chamber assay.
resultsOur results showed that both inhibitors had differential effects on the two cell lines, significantly reducing migration in the metastatic Y79 cell line and greatly affecting the viability of Weri-1 cells. The MMP-9 inhibitor (MMP9I) AG-L-66085, diminished the Y79 angiogenic response. In Weri-1 cells, VEGF was significantly reduced and cell viability was decreased by both MMP-2 and MMP-9 inhibitors. Furthermore, inhibition of MMP-2 significantly reduced secretion of TGF-β1 in both Rb models.
conclusionsCollectively, our data indicates MMP-2 and MMP-9 drive metastatic pathways, including migration, viability and secretion of angiogenic factors in Rb cells. These two subtypes of matrix metalloproteinases represent new potential candidates for targeted anti-metastatic therapy for Rb.
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