Interactions between CXCR4 and CXCL12 promote cell migration and invasion of canine hemangiosarcoma

K. S. Im, A. J. Graef, M. Breen, K. Lindblad-Toh, J. F. Modiano, J. H. Kim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The CXCR4/CXCL12 axis plays an important role in cell locomotion and metastasis in many cancers. In this study, we hypothesized that the CXCR4/CXCL12 axis promotes migration and invasion of canine hemangiosarcoma (HSA) cells. Transcriptomic analysis across 12 HSA cell lines and 58 HSA whole tumour tissues identified heterogeneous expression of CXCR4 and CXCL12, which was associated with cell movement. In vitro, CXCL12 promoted calcium mobilization, cell migration and invasion that were directly proportional to surface expression of CXCR4; furthermore, these responses proved sensitive to the CXCR4 antagonist, AMD3100, in HSA cell lines. These results indicate that CXCL12 potentiates migration and invasion of canine HSA cells through CXCR4 signalling. The direct relationship between these responses in HSA cells suggests that the CXCR4/CXCL12 axis contributes to HSA progression.

Original languageEnglish (US)
Pages (from-to)315-327
Number of pages13
JournalVeterinary and Comparative Oncology
Issue number2
StatePublished - Jun 2017

Bibliographical note

Funding Information:
The authors thank Dr Erin Dickerson for experimental advice and helpful discussions, Mitzi Lewellen for editorial assistance, Paul Champoux and Nisha Shah for technical assistance with flow cytometry experiments, Dr Aaron Sarver for advice in handling and managing bioinformatic data, Dr Douglas Thamm for review of the manuscript, the Minnesota Supercomputing Institute for computational resources and the University of Minnesota Genomic Center for assistance with implementation of genome-wide technologies. The authors disclose receipt of the following financial support for the research and/or authorship of this article: grant D13CA-400 from Morris Animal Foundation (J.-H. K.), grant 1759 from the AKC Canine Health Foundation (J. F. M.), grant D10CA-501 from the Golden Retriever Foundation and Morris Animal Foundation (J. F. M, M. B. and K. L. T.), grant 1889G from the Golden Retriever Foundation and the AKC Canine Health Foundation (J. F. M., M. B. and K. L. T.), grant DM06CO-003 from the National Canine Cancer Foundation (J. F. M.), and a Translational Sarcoma Research Award from the Masonic Cancer Center, University of Minnesota and the Children's Cancer Research Fund (J. F. M.). The National Institutes of Health Comprehensive Cancer Center Support Grant to the Masonic Cancer Center (P30 CA077598) provided support for bioinformatics, genomics and flow cytometry services. The authors also gratefully acknowledge support from donors to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project.

Publisher Copyright:
© 2015 John Wiley & Sons Ltd


  • CXCL12
  • CXCR4
  • canine hemangiosarcoma
  • invasion
  • migration


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