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Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model
- Publication Year :
- 2017
- Publisher :
- Taylor & Francis, 2017.
-
Abstract
- Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC. Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes. Histopathological scoring was performed at 12 weeks of age and 23 weeks of age. Gene expression of macrophage markers and inflammatory mediators were measured in the mammary gland and tumor microenvironment at sacrifice. As expected, MCP-1 depletion resulted in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression represented by histopathological scoring (12 weeks of age). Deficiency in MCP-1 significantly downregulated expression of macrophage markers in the mammary gland (Mertk and CD64) and the tumor microenvironment (CD64), and also reduced expression of inflammatory cytokines in the mammary gland (TNFα and IL-1β) and the tumor microenvironment (IL-6). These data support the hypothesis that MCP-1 expression contributes to increased tumorigenesis in a model of TNBC via recruitment of macrophages and subsequent increase in inflammatory mediators.
- Subjects :
- 0301 basic medicine
Cancer Research
Genotype
Carcinogenesis
Mammary gland
Triple Negative Breast Neoplasms
Biology
medicine.disease_cause
Monocytes
Proinflammatory cytokine
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Tumor Microenvironment
Animals
Humans
Pharmacology
Inflammation
Tumor microenvironment
Macrophages
Cancer
Mammary Neoplasms, Experimental
medicine.disease
Primary tumor
Tumor Burden
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Oncology
Tumor progression
030220 oncology & carcinogenesis
Immunology
Molecular Medicine
Tumor necrosis factor alpha
Female
Research Paper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....36566afeb746b25b38332f8a0428c016