title: Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model.
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.
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Cranford
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Kandy T
authors.initials: KT
authors.lastname: Velázquez
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Jackie E
authors.initials: JE
authors.lastname: Bader
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Carson
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Ioulia
authors.initials: I
authors.lastname: Chatzistamou
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.affiliation: a Department of Pathology , Microbiology & Immunology, School of Medicine, University of South Carolina , Columbia , SC , USA.
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment
keywords: Inflammation; macrophages; mammary tumorigenesis; monocyte chemoattractant protein; triple negative breast cancer