ArticleCancer research2010
Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface.
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 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Common polymorphism in the MMP-13 gene may contribute to the risk of human cancers: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
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- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- The integrin α2-osteoclast axis: a key driver of bone destruction and therapeutic target in osteosarcoma.Journal of translational medicine · 2025Article
- Single-Cell Analysis Reveals that Vitamin C Inhibits Bone Metastasis of Renal Cancer via Cell Cycle Arrest and Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling Matrix Metalloproteinase 13's Dynamic Role in Breast Cancer: A Link to Physical Changes and Prognostic Modulation.International journal of molecular sciences · 2025Review
- Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan.Life (Basel, Switzerland) · 2024Article
- Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines.iScience · 2024Article
- Redefining metalloproteases specificity through network proteolysis.Trends in molecular medicine · 2024Review
- Tripartite motif-containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis.Journal of cell communication and signaling · 2023Article
- Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges.Pharmaceutics · 2023Review
- Upregulated SSB Is Involved in Hepatocellular Carcinoma Progression and Metastasis through the Epithelial-Mesenchymal Transition, Antiapoptosis, and Altered ROS Level Pathway.Oxidative medicine and cellular longevity · 2023Article
- Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus.Frontiers in cell and developmental biology · 2023Article
- Regulation and Function of Matrix Metalloproteinase-13 in Cancer Progression and Metastasis.Cancers · 2022Review
- Caveolin-1-Derived Peptide Reduces ER Stress and Enhances Gelatinolytic Activity in IPF Fibroblasts.International journal of molecular sciences · 2022Article
- Matrix metalloproteinases as therapeutic targets in breast cancer.Frontiers in oncology · 2022Review
- GPNMB overexpression is associated with extensive bone metastasis and poor prognosis in renal cell carcinoma.Oncology letters · 2022Article
- Transcriptome Profiling of Osteoblasts in a Medaka (Frontiers in cell and developmental biology · 2022Article
- Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.Bioscience reports · 2021Article
- Targeting integrin αvβ3 with indomethacin inhibits patient-derived xenograft tumour growth and recurrence in oesophageal squamous cell carcinoma.Clinical and translational medicine · 2021Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The tropism of breast cancer cells for bone and their tendency to induce an osteolytic phenotype are a result of interactions between breast cancer cells and stromal cells and are of paramount importance for bone metastasis. However, the underlying molecular mechanisms remain poorly understood. We hypothesize that tumor-stromal interaction alters gene expression in malignant tumor cells and stromal cells creating a unique expression signature that promotes osteolytic breast cancer bone metastasis and that inhibition of such interactions can be developed as targeted therapeutics. Microarray analysis was performed to investigate gene expression profiling at the tumor-bone (TB) interface versus the tumor alone area from syngenic mice injected with three different syngenic mammary tumor cell lines that differ in their metastatic potential. We identified matrix metalloproteinase 13 (MMP13), receptor activator of NF-kappaB ligand (RANKL), and integrins binding sialoprotein to be genes upregulated at the TB interface and validated. To determine the functional role of MMP13 in tumor-induced osteolysis, mice with Cl66 mammary tumors were treated with MMP13 antisense oligonucleotides (MMP13-ASO) or control scrambled oligonucleotides (control-ASO). Knockdown of MMP13 expression at the TB interface leads to significant reduction in bone destruction and in the number of activated osteoclasts at the TB interface. Further analysis to evaluate the mechanism of MMP13-dependent osteolytic bone metastasis revealed that MMP13-ASO treatment decreased active MMP9, RANKL levels, and transforming growth factor-beta signaling at the TB interface. Together, our data indicate that upregulation of MMP13 at the TB interface is important in tumor-induced osteolysis and suggest that MMP13 is a potential therapeutic target for breast cancer bone metastasis.
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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.