ArticleThe Journal of clinical investigation2008
The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.
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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
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 377 citations in OpenAlex.
- Rethinking ovarian cancer: recommendations for improving outcomes.Nature reviews. Cancer · 2011Guideline
- The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause.Aging cell · 2026Article
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- A Dual-Action Gold(I) Prodrug Targeting Redox Homeostasis and Extracellular Matrix Remodeling in Ovarian Cancer.ACS medicinal chemistry letters · 2026Article
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Stem cell-directed targeted chemotherapy primes drug-resistant metastatic ovarian tumors for elimination by natural killer cells.Molecular therapy. Oncology · 2026Article
- DCLK1 regulates stemness and IL-6/STAT3-dependent metastatic niche formation in chemoresistant ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?Cancer medicine · 2026Review
- Natural compounds targeting glycolysis and TME in ovarian cancer: from metabolic crosstalk to therapeutic potential.Frontiers in pharmacology · 2026Review
- Mapping transcriptomic signatures downstream of mitochondrial superoxide dismutase SOD2 in OVCA433 multicellular aggregates.Advances in redox research · 2025Article
- The Role of CAF-derived Vitronectin in Promoting Colorectal Cancer Progression and Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression.Cancer cell · 2025Article
- Review
- Collagen fiber density observed in metastatic ovarian cancer promotes tumor cell adhesion.Acta biomaterialia · 2025Article
- Identification of vitronectin as a potential non-invasive biomarker of metastatic breast cancer using a label-free LC-MS/MS approach.Breast cancer research : BCR · 2025Article
- Review
- Regulating the expression of matrix metalloproteinases to inhibit ovarian carcinoma using isoquinoline alkaloid from Allium ascalonicum.Scientific reports · 2025Article
- Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis.Cancer research · 2024Article
- Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness.Cell death & disease · 2024Article
- ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer.Molecular cancer research : MCR · 2024Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Most patients (80%) with ovarian cancer (OvCa) present with metastatic disease. Attachment of OvCa cells to peritoneum and omentum represents the first rate-limiting step for metastatic spread. Therefore, identifying factors regulating cell attachment in the abdominal cavity is critical to the development of therapeutic agents. We show here that MMP-2 expression was upregulated in OvCa cells upon attachment to their microenvironment. Downregulation of MMP-2 mRNA or pharmacological inhibition of MMP-2 proteolytic function, in both human OvCa primary cells and cell lines, reduced attachment of OvCa cells to a 3D organotypic model of metastatic OvCa, full human omentum or peritoneum, and in vivo to mouse peritoneum and omentum. Absence of MMP-2 in the host did not alter OvCa adhesion, as determined utilizing mice harboring homozygous null mutations in either the Mmp2 or Mmp9 genes. Conversely, adhesion induced upregulation of MMP-2 mRNA in OvCa cells. MMP-2 inhibition in OvCa cells through pharmacological or antibody treatment prior to i.p. dissemination in nude mice significantly decreased tumor growth and metastasis and extended survival. MMP-2 enhanced peritoneal adhesion of OvCa cells through cleavage of ECM proteins fibronectin (FN) and vitronectin (Vn) into small fragments and increased binding of OvCa cells to these FN and Vn fragments and their receptors, alpha5beta1 and alphaVbeta3 integrin. These findings indicate that MMP-2 expressed by metastatic OvCa cells functionally regulates their attachment to peritoneal surfaces.
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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.