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Open Access Highly Accessed Research article

CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and invasion of canine mammary cancer cells

Magdalena Król1*, Kinga Majchrzak2, Joanna Mucha1, Agata Homa1, Małgorzata Bulkowska1, Arleta Jakubowska1, Malwina Karwicka1, Karol M Pawłowski3 and Tomasz Motyl1

Author Affiliations

1 Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, Warsaw, 02-776, Poland

2 Department of Animal Environment Biology, Faculty of Animal Sciences, Warsaw University of Life Sciences - WULS, Ciszewskiego 8, Warsaw, 02-786, Poland

3 Department of Large Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences – WULS, Nowoursynowska 100, Warsaw, 02-797, Poland

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BMC Veterinary Research 2013, 9:65  doi:10.1186/1746-6148-9-65

Published: 5 April 2013

Abstract

Background

Tumor-associated macrophages (TAMs) have high impact on the cancer development because they can facilitate matrix invasion, angiogenesis, and tumor cell motility. It gives cancer cells the capacity to invade normal tissues and metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which is an important regulator of proliferation and differentiation of monocytes and macrophages regulates most of the tissue macrophages. However, CSF-1R is expressed also in breast epithelial tissue during some physiological stages i.g.: pregnancy and lactation. Its expression has been also detected in various cancers. Our previous study has showed the expression of CSF-1R in all examined canine mammary tumors. Moreover, it strongly correlated with grade of malignancy and ability to metastasis. This study was therefore designed to characterize the role of CSF-1R in canine mammary cancer cells proliferation, apoptosis, migration, and invasion. As far as we know, the study presented hereby is a pioneering experiment in this field of veterinary medicine.

Results

We showed that csf-1r silencing significantly increased apoptosis (Annexin V test), decreased proliferation (measured as Ki67 expression) and decreased migration (“wound healing” assay) of canine mammary cancer cells. Treatment of these cells with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth characteristics of highly invasive cell lines on Matrigel matrix, and significantly decreased the ability of these cells to invade matrix. CSF-1 treatment increased invasion of cancer cells.

Conclusion

The evidence of the expression and functional role of the CSF-1R in canine mammary cancer cells indicate that CSF-1R targeting may be a good therapeutic approach.

Keywords:
Canine mammary carcinoma; CSF-1R; Tumor-associated macrophages; Tumor microenvironment