Inking tumor-associated macrophages, inflammation, and intestinal tumorigenesis

Role of MCP-1

Jamie L. McClellan, J. Mark Davis, Jennifer L. Steiner, Reilly T. Enos, Seung H. Jung, James Carson, Maria M. Pena, Kevin A. Carnevale, Franklin G. Berger, E. Angela Murphy

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Tumor-associated macrophages are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. However, its role on tumorigenesis in a genetic mouse model of colon cancer has not been explored. We examined the role of MCP-1 on tumor-associated macrophages, inflammation, and intestinal tumorigenesis. Male Apc Min/+ , Apc Min/+ /MCP-1 -/- or wild-type mice were euthanized at 18 wk of age and intestines were analyzed for polyp burden, apoptosis, proliferation, β-catenin, macrophage number and phenotype, markers for cytotoxic T lymphocytes and regulatory T cells, and inflammatory mediators. MCP-1 deficiency decreased overall polyp number by 20% and specifically large polyp number by 45% (P < 0.05). This was consistent with an increase in apoptotic cells (P < 0.05), but there was no change detected in proliferation or β-catenin. MCP-1 deficiency decreased F4/80-positive cells in both the polyp tissue and surrounding intestinal tissue (P < 0.05) as well as expression of markers associated with M1 (IL-12 and IL-23) and M2 macrophages (IL-13, CD206, TGF-β, and CCL17) (P < 0.05). MCP-1 knockout was also associated with increased cytotoxic T lymphocytes and decreased regulatory T cells (P < 0.05). In addition, MCP-1 -/- offset the increased mRNA expression of IL-1β and IL-6 in intestinal tissue and IL-1β and TNF-α in polyp tissue (P < 0.05), and prevented the decrease in SOCS1 expression (P < 0.05). We demonstrate that MCP-1 is an important mediator of tumor growth and immune regulation that may serve as an important biomarker and/or therapeutic target in colon cancer.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number10
DOIs
StatePublished - Nov 15 2012
Externally publishedYes

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Chemokine CCL2
Carcinogenesis
Macrophages
Inflammation
Polyps
Neoplasms
Catenins
Protein Deficiency
Cytotoxic T-Lymphocytes
Regulatory T-Lymphocytes
Interleukin-1
Colonic Neoplasms
Interleukin-23
Tumor Microenvironment
Interleukin-13
Genetic Models
Interleukin-12
Chemokines
Intestines
Interleukin-6

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Inking tumor-associated macrophages, inflammation, and intestinal tumorigenesis : Role of MCP-1. / McClellan, Jamie L.; Mark Davis, J.; Steiner, Jennifer L.; Enos, Reilly T.; Jung, Seung H.; Carson, James; Pena, Maria M.; Carnevale, Kevin A.; Berger, Franklin G.; Angela Murphy, E.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 303, No. 10, 15.11.2012.

Research output: Contribution to journalArticle

McClellan, JL, Mark Davis, J, Steiner, JL, Enos, RT, Jung, SH, Carson, J, Pena, MM, Carnevale, KA, Berger, FG & Angela Murphy, E 2012, 'Inking tumor-associated macrophages, inflammation, and intestinal tumorigenesis: Role of MCP-1', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 303, no. 10. https://doi.org/10.1152/ajpgi.00252.2012
McClellan, Jamie L. ; Mark Davis, J. ; Steiner, Jennifer L. ; Enos, Reilly T. ; Jung, Seung H. ; Carson, James ; Pena, Maria M. ; Carnevale, Kevin A. ; Berger, Franklin G. ; Angela Murphy, E. / Inking tumor-associated macrophages, inflammation, and intestinal tumorigenesis : Role of MCP-1. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2012 ; Vol. 303, No. 10.
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