ArticleMolecular cancer research : MCR2010
Tissue inhibitor of metalloproteinase-2 regulates matrix metalloproteinase-2-mediated endothelial barrier dysfunction and breast cancer cell transmigration through lung microvascular endothelial cells.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 65 citations in OpenAlex.
- Bioinformatic Analysis of Contrasting Expression Patterns and Molecular Interactions of TIMPs in Breast Cancer: Implications for Tumor Progression and Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Extracellular vesicles delivering TIMP-2 modulate MMP-1, MMP-2, and MMP-9 expression in human lung adenocarcinoma A549 cells.Frontiers in pharmacology · 2026Article
- Inhibition of Notch enhances efficacy of immune checkpoint blockade in triple-negative breast cancer.Science advances · 2024Article
- The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.Breast cancer research : BCR · 2024Article
- Article
- Nitric Oxide-Scavenging, Anti-Migration Effects, and Glycosylation Changes after Hemin Treatment of Human Triple-Negative Breast Cancer Cells: A Mechanistic Study.ACS pharmacology & translational science · 2023Article
- TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer.Journal of cancer research and clinical oncology · 2023Article
- Imbalance of Pulmonary Microvascular Endothelial Cell-Expression of Metalloproteinases and Their Endogenous Inhibitors Promotes Septic Barrier Dysfunction.International journal of molecular sciences · 2023Article
- Matrix metalloproteinases as therapeutic targets in breast cancer.Frontiers in oncology · 2022Review
- DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma.Scientific reports · 2021Article
- Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events.Genes · 2021Article
- A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier.Cancer research · 2021Article
- TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells.BMC cancer · 2020Article
- Molecular and functional extracellular vesicle analysis using nanopatterned microchips monitors tumor progression and metastasis.Science translational medicine · 2020Article
- Matrisome-Associated Gene Expression Patterns Correlating with TIMP2 in Cancer.Scientific reports · 2019Article
- p85α Inactivates MMP-2 and Suppresses Bladder Cancer Invasion by Inhibiting MMP-14 Transcription and TIMP-2 Degradation.Neoplasia (New York, N.Y.) · 2019Article
- Targeting the MMP-14/MMP-2/integrin αThe Journal of biological chemistry · 2018Article
- Article
- Extracellular Vesicles: Packages Sent With Complement.Frontiers in immunology · 2018Review
- Gene delivery nanoparticles to modulate angiogenesis.Advanced drug delivery reviews · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Matrix metalloproteinases (MMP) have been implicated in multiple stages of cancer metastasis. Tissue inhibitor of metalloproteinase-2 (TIMP-2) plays an important role in regulating MMP-2 activity. By forming a ternary complex with pro-MMP-2 and its activator MMP-14 on the cell surface, TIMP-2 can either initiate or restrain the cleavage and subsequent activation of MMP-2. Our recent work has shown that breast cancer cell adhesion to vascular endothelial cells activates endothelial MMP-2, promoting tumor cell transendothelial migration (TEM(E)). However, the mechanism of MMP-2 regulation during TEM(E) remains unclear. In the current study, we present evidence that MMP-14 is expressed in both invasive breast cancer cells (MDA-MB-231 and MDA-MB-436) and lung microvascular endothelial cells (HBMVEC-L), whereas TIMP-2 is exclusively expressed and released from the cancer cells. The tumor cell-derived TIMP-2 was further identified as a major determinant of endothelial MMP-2 activity during tumor cell transmigration in the presence of MMP-14. This response was associated with endothelial barrier dysfunction because coculture of MDA-MB-231 or MDA-MB-436 with HBMVEC-L caused a significant decrease in transendothelial electrical resistance concomitantly with endothelial cell-cell junction disruption and tumor cell transmigration. Knockdown of TIMP-2 or inhibition of TIMP-2/MMP-14 attenuated MMP-2-dependent transendothelial electrical resistance response and TEM(E). These findings suggest a novel interactive role of breast cancer cells and vascular endothelial cells in regulating the TIMP-2/MMP-14/MMP-2 pathway during tumor metastasis.
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