Interactions between CXCR4 and CXCL12 promote cell migration and invasion of canine hemangiosarcoma.
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.
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
K S
KS
Im
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
A J
AJ
Graef
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, & Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA.|Cancer Genetics Program, University of North Carolina Lineberger Comprehensive Cancer Center, Raleigh, NC, USA.
M
M
Breen
Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Science for Life Laboratory, Dept. of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
K
K
Lindblad-Toh
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.|Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
J F
JF
Modiano
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
J-H
JH
Kim
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000502:physiology*; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D020869:Gene Expression Profiling / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006394:Hemangiosarcoma / Q000473:pathology / Q000662:veterinary*; D009361:Neoplasm Invasiveness / Q000473:pathology; D019718:Receptors, CXCR4 / Q000502:physiology*
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
CXCL12; CXCR4; canine hemangiosarcoma; invasion; migration