Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated

Marta Torroella-Kouri, Risset Silvera, Dayron Rodriguez, Raul Caso, Alwi Shatry, Shannon Opiela, Dan Ilkovitch, Reto A. Schwendener, Vijaya Iragavarapu-Charyulu, Yoslayma Cardentey, Natasa Strbo, Diana M Lopez

Research output: Contribution to journalArticle

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Abstract

Systemic and local immune deficiency is associated with cancer, and the role of M2 tumor-associated macrophages in this phenomenon is well recognized. However, the immune status of macrophages from peripheral compartments in tumor hosts is unclear. Peritoneal macrophages (PEM)are derived from circulating monocytes and recruited to the peritoneal cavity where they differentiate into macrophages. We have previously shown that PEMs from mice bearing D1-DMBA-3 mammary tumors (T-PEM)ar e deficient in inflammatory functions and that this impairment is associated with diminished expression of transcription factors nuclear factor κB and CAAT/enhancer-binding protein. We now provide evidence that T-PEMs display neither M1 nor M2 phenotypes, yet exhibit deficiencies in the expression of several inflammatory cytokines and various proinflammatory signaling pathways. Moreover, due to nuclear factor κB downregulation, increased apoptosis was observed in T-PEMs. We report for the first time that macrophage depletion is associated with increased macrophage progenitors in bone marrow. Furthermore, T-PEMs have a lower expression of macrophage differentiation markers F4/80, CD68, CD115, and CD11b, whereas Gr-1 is up-regulated. Our results suggest that T-PEMs are less differentiated and represent a newly derived population from blood monocytes. Lastly, we show that transforming growth factor-B and prostaglandin E2, two immunosuppressive tumor-derived factors, may be involved in this phenomenon.

Original languageEnglish
Pages (from-to)4800-4809
Number of pages10
JournalCancer Research
Volume69
Issue number11
DOIs
StatePublished - Jun 1 2009

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Macrophages
Breast Neoplasms
Peritoneal Macrophages
Monocytes
Neoplasms
CCAAT-Enhancer-Binding Proteins
9,10-Dimethyl-1,2-benzanthracene
Differentiation Antigens
Peritoneal Cavity
Transforming Growth Factors
Immunosuppressive Agents
Dinoprostone
Transcription Factors
Down-Regulation
Bone Marrow
Apoptosis
Cytokines
Phenotype
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. / Torroella-Kouri, Marta; Silvera, Risset; Rodriguez, Dayron; Caso, Raul; Shatry, Alwi; Opiela, Shannon; Ilkovitch, Dan; Schwendener, Reto A.; Iragavarapu-Charyulu, Vijaya; Cardentey, Yoslayma; Strbo, Natasa; Lopez, Diana M.

In: Cancer Research, Vol. 69, No. 11, 01.06.2009, p. 4800-4809.

Research output: Contribution to journalArticle

Torroella-Kouri, M, Silvera, R, Rodriguez, D, Caso, R, Shatry, A, Opiela, S, Ilkovitch, D, Schwendener, RA, Iragavarapu-Charyulu, V, Cardentey, Y, Strbo, N & Lopez, DM 2009, 'Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated', Cancer Research, vol. 69, no. 11, pp. 4800-4809. https://doi.org/10.1158/0008-5472.CAN-08-3427
Torroella-Kouri, Marta ; Silvera, Risset ; Rodriguez, Dayron ; Caso, Raul ; Shatry, Alwi ; Opiela, Shannon ; Ilkovitch, Dan ; Schwendener, Reto A. ; Iragavarapu-Charyulu, Vijaya ; Cardentey, Yoslayma ; Strbo, Natasa ; Lopez, Diana M. / Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. In: Cancer Research. 2009 ; Vol. 69, No. 11. pp. 4800-4809.
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