ArticleMolecular cancer therapeutics2012
A locked, dimeric CXCL12 variant effectively inhibits pulmonary metastasis of CXCR4-expressing melanoma cells due to enhanced serum stability.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 52 citations in OpenAlex.
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- Regulating Chemokine-Receptor Interactions through the Site-Specific Bioorthogonal Conjugation of Photoresponsive DNA Strands.Bioconjugate chemistry · 2023Article
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Prospects for targeting ACKR1 in cancer and other diseases.Frontiers in immunology · 2023Review
- The Extended N-Terminal Domain Confers Atypical Chemokine Receptor Properties to CXCR3-B.Frontiers in immunology · 2022Article
- Tumour angiogenesis normalized by myo-inositol trispyrophosphate alleviates hypoxia in the microenvironment and promotes antitumor immune response.Journal of cellular and molecular medicine · 2021Article
- Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance.NPJ precision oncology · 2021Article
- The chemokine X-factor: Structure-function analysis of the CXC motif at CXCR4 and ACKR3.The Journal of biological chemistry · 2020Article
- Natural and engineered chemokine (C-X-C motif) receptor 4 agonists prevent acute respiratory distress syndrome after lung ischemia-reperfusion injury and hemorrhage.Scientific reports · 2020Article
- Chemokines in COPD: From Implication to Therapeutic Use.International journal of molecular sciences · 2019Review
- The Solution Structure of CCL28 Reveals Structural Lability that Does Not Constrain Antifungal Activity.Journal of molecular biology · 2018Article
- Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3.British journal of pharmacology · 2018Article
- Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers.Frontiers in immunology · 2018Review
- Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle.Open biology · 2018Article
- Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Chemokines from a Structural Perspective.International journal of molecular sciences · 2017Review
- Removal of a consensus proline is not sufficient to allow tetratricopeptide repeat oligomerization.Protein science : a publication of the Protein Society · 2017Article
- Enriching Traditional Protein-protein Interaction Networks with Alternative Conformations of Proteins.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The CXC chemokine receptor-4 (CXCR4) plays a critical role in cancer by positively regulating cancer cell metastasis and survival. We previously showed that high concentrations of the CXCR4 ligand, wild-type CXCL12 (wtCXCL12), could inhibit colorectal cancer metastasis in vivo, and we have hypothesized that wtCXCL12 dimerizes at high concentration to become a potent antagonist of CXCR4. To address this hypothesis, we engineered a covalently locked, dimeric variant of CXCL12 (CXCL122). Herein, we show that CXCL122 can not only inhibit implantation of lung metastasis of CXCR4-B16-F10 melanoma cells more effectively than AMD3100, but that CXCL122 also blocks the growth of established pulmonary tumors. To identify a basis for the in vivo efficacy of CXCL122, we conducted Western blot analysis and ELISA analyses, which revealed that CXCL122 was stable for at least 12 hours in serum, whereas wtCXCL12 was quickly degraded. CXCL122 also maintained its antagonist properties in in vitro chemotaxis assays for up to 24 hours in serum, whereas wtCXCL12 was ineffective after 6 hours. Heat-inactivation of serum prolonged the stability and function of wtCXCL12 by more than 6 hours, suggesting enzymatic degradation as a possible mechanism for wtCXCL12 inactivation. In vitro analysis of amino-terminal cleavage by enzymes dipeptidylpeptidase IV (DPPIV/CD26) and matrix metalloproteinase-2 (MMP-2) resulted in 25-fold and 2-fold slower degradation rates, respectively, of CXCL122 compared with wtCXCL12. In summary, our results suggest CXCL122 possesses greater potential as an antimetastatic drug as compared with AMD3100 or wtCXCL12, potentially due to enhanced serum stability in the presence of N-terminal degrading enzymes.
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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.