ArticleCancer research2010
Identification of a metalloprotease-chemokine signaling system in the ovarian cancer microenvironment: implications for antiangiogenic therapy.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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.
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Who cites it
63 citing papers in PubMed, 115 citations in OpenAlex.
- A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function.Acta pharmaceutica Sinica. B · 2026Article
- Review
- Matrix Metalloproteinases 1 and 3 in Ovarian Cancer: Diagnostic and Prognostic Potential of Genetic Variants and Expression Profiling.Diagnostics (Basel, Switzerland) · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- GPCRs and fibroblast heterogeneity in fibroblast-associated diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Review
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Review
- Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- Chemokine expression in patients with ovarian cancer or benign ovarian tumors.Archives of medical science : AMS · 2022Article
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.Cell death discovery · 2021Article
- Review
- The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance.International journal of molecular sciences · 2021Review
- Approaches Toward Targeting Matrix Metalloproteases for Prognosis and Therapies in Gynecological Cancer: MicroRNAs as a Molecular Driver.Frontiers in oncology · 2021Review
- Molecular mediators of peritoneal metastasis in pancreatic cancer.Cancer metastasis reviews · 2020Review
- IL-8 promotes cell migration through regulating EMT by activating the Wnt/β-catenin pathway in ovarian cancer.Journal of cellular and molecular medicine · 2020Article
- Identification of potential hub genes associated with the pathogenesis and prognosis of pancreatic duct adenocarcinoma using bioinformatics meta-analysis of multi-platform datasets.Oncology letters · 2019Article
- Fluid shear stress-induced IL-8/CXCR signaling in human ovarian cancer cells.Translational cancer research · 2019Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Ovarian cancer is a lethal gynecologic malignancy that may benefit from new therapies that block key paracrine pathways involved in tumor-stromal interactions and tumor vascularity. It was recently shown that matrix metalloprotease-1 (MMP1) activation of the G protein-coupled receptor protease-activated receptor-1 (PAR1) is an important stimulator of angiogenesis and metastasis in peritoneal mouse models of ovarian cancer. In the present study, we tested the hypothesis that MMP1-PAR1 promotes angiogenesis through its paracrine control of angiogenic chemokine receptors. We found that MMP1-PAR1 activation induces the secretion of several angiogenic factors from ovarian carcinoma cells, most prominently interleukin (IL)-8, growth-regulated oncogene-alpha (GRO-alpha), and monocyte chemoattractant protein-1. The secreted IL-8 and GRO-alpha acts on endothelial CXCR1/2 receptors in a paracrine manner to cause robust endothelial cell proliferation, tube formation, and migration. A cell-penetrating pepducin, X1/2pal-i3, which targets the conserved third intracellular loop of both CXCR1 and CXCR2 receptors, significantly inhibited endothelial cell proliferation, tube formation, angiogenesis, and ovarian tumor growth in mice. Matrigel plugs mixed with MMP1-stimulated, OVCAR-4-conditioned media showed a dramatic 33-fold increase in blood vessel formation in mice. The X1/2pal-i3 pepducin completely inhibited MMP1-dependent angiogenesis compared with a negative control pepducin or vehicle. Conversely, a vascular endothelial growth factor-directed antibody, Avastin, suppressed angiogenesis in mice but, as expected, was unable to inhibit IL-8 and GRO-alpha-dependent endothelial tube formation in vitro. These studies identify a critical MMP1-PAR1-CXCR1/2 paracrine pathway that might be therapeutically targeted for ovarian cancer treatment.
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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.