ArticlePloS one2011
Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
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- Osteopontin regulates the growth and invasion of liver cancer cells via DTL.Oncology letters · 2023Article
- Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma.Biomedicines · 2023Article
- Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review.International journal of molecular sciences · 2023Review
- The Intracellular and Secreted Sides of Osteopontin and Their Putative Physiopathological Roles.International journal of molecular sciences · 2023Review
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- Combination therapy of cisplatin and resveratrol to induce cellular aging in gastric cancer cells: Focusing on oxidative stress, and cell cycle arrest.Frontiers in pharmacology · 2022Article
- Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases.Biomedicines · 2021Review
- Investigation of the Osteopontin isoforms expression in patients with acute myeloid leukemia.Medical oncology (Northwood, London, England) · 2021Article
- Targeting the hallmarks of cancer: the effects of silibinin on proliferation, cell death, angiogenesis, and migration in colorectal cancer.BMC complementary medicine and therapies · 2021Article
- Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases.International journal of molecular sciences · 2021Review
- Osteopontin Takes Center Stage in Chronic Liver Disease.Hepatology (Baltimore, Md.) · 2021Review
- Article
- Review
- The effect of bone marrow mesenchymal stem cells on highly metastatic MHCC97-H hepatocellular carcinoma cells following OPN and TGFβ1 gene silencing.Experimental and therapeutic medicine · 2020Article
- In vitro and bioinformatics mechanistic-based approach for cadmium carcinogenicity understanding.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Cytotoxicity and cell death induced by engineered nanostructures (quantum dots and nanoparticles) in human cell lines.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- CD44 in Ovarian Cancer Progression and Therapy Resistance-A Critical Role for STAT3.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsOsteopontin, SDF-1α, and MMP-2 are important secreted molecules involved in the pathophysiology of human hepatocellular carcinoma (HCC). This study investigates the effect of the SDF-1α/CXCR4 axis on expression and activity of MMP-2 induced by osteopontin.
methodsThe expression of CXCR4, SDF-1α, MMP-2 and their associated cellular signaling cascades, involving Akt and MAP Kinases, were determined by Western blotting. The activities of MMP-2 and MMP-9 were assayed by gel zymography. The role of the osteopontin receptors integrin α(v)β₃ and CD44v6 was evaluated using neutralizing antibodies. We also established CXCR4-deficient SMMC7721 cell lines by transfection with miRNA-CXCR4 plasmids and determined cell invasion activity in a transwell assay.
resultsIn comparison with untreated cells, recombinant human osteopontin (rhOPN) up-regulated CXCR4, SDF-1α, and MMP-2 expression about 5-, 4-, and 6-fold on the protein levels through binding to integrin α(v)β₃ and CD44v6 in hepatocellular carcinoma cells (SMMC7721 and HepG2). Inhibition of the SDF-1α/CXCR4 axis down-regulated the rhOPN-induced MMP-2 expression and activity. rhOPN also activated Akt, p38 and JNK. Down-regulation of CXCR4 decreased the rhOPN-induced invasion in SMMC7721 cells.
conclusionThese results indicate that rhOPN up-regulates MMP-2 through the SDF-1α/CXCR4 axis, mediated by binding to integrin α(v)β₃ and CD44v6 and activating the PI-3K/Akt and JNK pathways in HepG2 and SMMC7721 cells. Therefore, the osteopontin-SDF-1α/CXCR4-MMP-2 system may be a new therapeutic target for treating HCC progression.
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