ArticleClinical & experimental metastasis2007
MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2.
Article in Clinical & experimental metastasis, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 158 citations in OpenAlex.
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- The lncRNA DANCR promotes breast cancer brain metastasis by acting as a ceRNA for miR-758-3p to regulate PTGS2 expression.Acta biochimica et biophysica Sinica · 2025Article
- Genomic and immune profiling of breast cancer brain metastases.Acta neuropathologica communications · 2025Article
- Role of Extracellular Vesicles in the Pathogenesis of Brain Metastasis.Journal of extracellular biology · 2025Review
- [Analysis of Risk Factors for Meningeal Metastasis in Patients with Lung Adenocarcinoma Following Non-surgical Interventions].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- The research progress on meningeal metastasis in solid tumors.Discover oncology · 2025Review
- Identification of antimicrobial peptides from the Ambystoma mexicanum displaying antibacterial and antitumor activity.PloS one · 2025Article
- Secondary Analysis of Human Bulk RNA-Seq Dataset Suggests Potential Mechanisms for Letrozole Resistance in Estrogen-Positive (ER+) Breast Cancer.Current issues in molecular biology · 2024Article
- Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing.International journal of molecular sciences · 2023Article
- Ectopic expression of matrix metalloproteinases and filopodia extension via JNK activation are involved in the invasion of blood tumor cells in Drosophila mxc mutant.Genes to cells : devoted to molecular & cellular mechanisms · 2023Article
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers.International journal of molecular sciences · 2023Article
- MicroRNA 133A Regulates Cell Proliferation, Cell Migration, and Apoptosis in Colorectal Cancer by Suppressing CDH3 Expression.Journal of Cancer · 2023Article
- Mesenchymal Stem Cells Treatment Aggravates Tumor Growth Regardless Its Route of Administration: An In vivo Study.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Matrix metalloproteinases as therapeutic targets in breast cancer.Frontiers in oncology · 2022Review
- Anticancer Potential of Green Synthesized Silver Nanoparticles of the Soft CoralPharmaceutics · 2021Article
- Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling.Scientific reports · 2021Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Matrix metalloproteinase 2 (MMP2) is important in breast cancer (BC) invasion and metastasis. We previously reported that BC brain metastases, in a rat syngeneic model developed in our laboratory, have high expression and activity of MMP2. The MMP2 mechanism of action in the brain is still under intense scrutiny. To study the role of MMP2 in the development of BC brain metastasis we transfected ENU1564 rat mammary adenocarcinoma cells with tissue inhibitor of MMP2 (TIMP2). Animals inoculated with ENU1564-TIMP2 cells had decreased orthotopic tumor growth, decreased orthotopic metastatic behavior and did not develop brain metastases. These results were associated with decreased MMP2 activity, demonstrated by gel zymography. Mitogen activated protein kinase (MAPK) pathway components, such as ERK1/2, have been correlated to MMP expression and/or astrocyte activity. We found that BC brain metastases have peripheral astrocyte reactivity and higher expression of glial fibrillary acidic protein (GFAP) and phosphorylated-ERK1/2 (p-ERK1/2). Additionally, rat astrocyte-conditioned media increased in vitro invasion of ENU1564 cancer cells and increased expression of MMP2 and p-ERK1/2. Blockage of ERK1/2 phosphorylation by treatment with MEK inhibitor (PD98059) decreased the expression of MMP2 in cancer cells grown in rat astrocyte-conditioned media. Our results are highly suggestive that MMP2 plays a role in the development of BC metastases, in particular to the brain. Furthermore, our results suggest that astrocyte factors and the ERK1/2 signaling pathway may be associated with BC brain metastasis development; and that ERK1/2 may regulate MMP2 in a way that is modifiable by astrocyte factors.
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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.