2. Academic Validation
  3. CXCL12-CXCL4 heterodimerization prevents CXCL12-driven breast cancer cell migration

CXCL12-CXCL4 heterodimerization prevents CXCL12-driven breast cancer cell migration

  • Cell Signal. 2020 Feb;66:109488. doi: 10.1016/j.cellsig.2019.109488.
Khanh T P Nguyen 1,  Lawrence J Druhan 2,  Belinda R Avalos 2,  Li Zhai 3,  Lubica Rauova 4,  Irina V Nesmelova 5,  Didier Dréau 6
Affiliations

Affiliations

  • 1 Department of Biological Sciences, UNC Charlotte, Charlotte, NC, United States of America.
  • 2 Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, United States of America; Center for Biomedical Engineering and Science, UNC Charlotte, Charlotte, NC, United States of America.
  • 3 Department of Pediatrics, The Children's Hospital of Philadelphia, PA, United States of America.
  • 4 Department of Pediatrics, The Children's Hospital of Philadelphia, PA, United States of America; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
  • 5 Center for Biomedical Engineering and Science, UNC Charlotte, Charlotte, NC, United States of America; Department of Physics and Optical Science, UNC Charlotte, Charlotte, NC, United States of America.
  • 6 Department of Biological Sciences, UNC Charlotte, Charlotte, NC, United States of America; Center for Biomedical Engineering and Science, UNC Charlotte, Charlotte, NC, United States of America. Electronic address: ddreau@uncc.edu.
PMID: 31785332 DOI: 10.1016/j.cellsig.2019.109488
Abstract

Despite improvements in Cancer early detection and treatment, metastatic breast Cancer remains deadly. Current therapeutic approaches have very limited efficacy in patients with triple negative breast Cancer. Among the many mechanisms associated that contribute to Cancer progression, signaling through the CXCL12-CXCR4 is an essential step in Cancer cell migration. We previously demonstrated the formation of CXCL12-CXCL4 heterodimers (Carlson et al., 2013). Here, we investigated whether CXCL12-CXCL4 heterodimers alter tumor cell migration. CXCL12 alone dose-dependently promoted the MDA-MB 231 cell migration (p < .05), which could be prevented by blocking the CXCR4 receptor. The addition of CXCL4 inhibited the CXCL12-induced cell migration (p < .05). Using NMR spectroscopy, we identified the CXCL4-CXCL12 binding interface. Moreover, we generated a CXCL4-derived peptide homolog of the binding interface that mimicked the activity of native CXCL4 protein. These results confirm the formation of CXCL12-CXCL4 heterodimers and their inhibitory effects on the migration of breast tumors cells. These findings suggest that specific Peptides mimicking heterodimerization of CXCL12 might prevent breast Cancer cell migration.

Keywords

Breast cancer cell migration; CXCL12; CXCL4; CXCR3; CXCR4; NMR.

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