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Abstract
Background: Canine mammary carcinoma is the most common cancer in female dogs and is often fatal due to the development of distance metastasis. The microenvironment of a tumour often contains abundant infiltrates of macrophages called tumour-associated macrophages (TAMs). TAMs express an activated phenotype, termed M2, which sustains proliferation of cancer cells, and has been correlated with poor clinical outcomes in human cancer patients. Cancer cells themselves have been implicated in stimulating the conversion of macrophages to a TAM with an M2 phenotype. This process has yet to be fully elucidated. Here we investigate the interplay between cancer cells and macrophages in the context of canine mammary carcinoma. Results: We show that cancer cells inhibit lipopolysaccharide (LPS)-induced macrophage activation. Further, we show that macrophage associated proteins, colony-stimulating factor (CSF)-1 and C-C motif ligand (CCL)-2, stimulate macrophages and are responsible for the effects of cancer cells on macrophages. We suggest the existence of a feedback loop between macrophages and cancer cells; while cancer cells influence the phenotype of the TAMs through CSF-1 and CCL2, the macrophages induce canine mammary cancer cells to upregulate their own expression of the receptors for CSF-1 and CCL2 and increase the cancer cellular metabolic activity. However, these cytokines in isolation induce a phenotypic state in macrophages that is between M1 and M2 phenotypes. Conclusions: Overall, our results demonstrate the extent to which canine mammary carcinoma cells influence the macrophage phenotype and the relevance of a feedback loop between these cells, involving CSF-1 and CCL2 as important mediators.
Original language | English |
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Article number | 151 |
Journal | BMC Veterinary Research |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 15 Jul 2015 |
Keywords / Materials (for Non-textual outputs)
- CCL2
- CSF-1
- Dog
- Mammary
- Tumour-associated macrophages
- Twist-1
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Dive into the research topics of 'Canine mammary cancer cells direct macrophages toward an intermediate activation state between M1/M2'. Together they form a unique fingerprint.Projects
- 1 Finished
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Characterisation of primitive stem cell-like canince cancer cells : identification of therapeutic targets through genomics
Argyle, D., Hupp, T. & Wallace, M.
17/03/08 → 16/03/11
Project: Research
Profiles
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David Argyle
- College of Medicine and Veterinary Medicine - Vice Principal and Head of College of Medicine & Veterinary
Person: Academic: Research Active