Blood monocytes from mammary tumor-bearing mice

Early targets of tumor-induced immune suppression?

Raul Caso, Risset Silvera, Roberto Carrio, Viyaya Iragavarapu-Charyulu, Ruben R. Gonzalez-Perez, Marta Torroella-Kouri

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have previously shown that peritoneal macrophages from mice bearing advanced D1-DMBA3 mammary tumors are impaired in their inflammatory functions but are not alternatively activated either and are less differentiated than the ones from normal mice. However, little is known about whether similar defects exist in their precursor stages as blood monocytes. We examined if blood monocytes from mammary tumor-bearing mice are already altered in their activation profiles before becoming macrophages and whether they correspond to inflammatory or resident monocyte subtypes. Much effort is currently devoted to reversing macrophage adverse traits in tumor hosts; as these cells reside within tissues, access is limited. Blood monocytes could be better targeted and manipulated by less invasive means. In the present study, mononuclear cells were isolated from whole blood of D1-DMBA-3 mammary tumor-bearing and normal BALB/c mice and CD115+ monocytes were analyzed. Our results show that there is an increase in circulating monocytes in tumor hosts; these monocytes exhibit a reduced expression of several myeloid differentiation markers such as CD115, F4/80, CD68 and CD11b. Moreover, downregulation of MHC II, CD62L and the proangiogenic marker Tie-2 are observed in these cells, whereas Gr-1 and Ly6C are upregulated. Furthermore, gene microarray analysis performed for the first time in blood monocytes from tumor hosts indicates that they express a mixture of pro-inflammatory and anti-inflammatory cytokines and chemokines. Interestingly, CCR2 and CX3CR1, which are crucial in monocyte definition as inflammatory or resident, respectively, are both upregulated. Importantly, complement proteins are enhanced whereas nitric oxide production is decreased and there is no measurable arginase activity detected in these cells. Collectively, our study represents the first comprehensive analysis of blood monocytes from tumor-bearing mice; we conclude that these cells are neither completely inflammatory nor suppressive and are less differentiated, similar to the macrophages they later become.

Original languageEnglish
Pages (from-to)891-900
Number of pages10
JournalInternational Journal of Oncology
Volume37
Issue number4
DOIs
StatePublished - Oct 1 2010

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Monocytes
Breast Neoplasms
Neoplasms
Macrophages
Arginase
9,10-Dimethyl-1,2-benzanthracene
Differentiation Antigens
Peritoneal Macrophages
Microarray Analysis
Chemokines
Complement System Proteins
Nitric Oxide
Anti-Inflammatory Agents
Down-Regulation
Cytokines
Genes

Keywords

  • Immune suppression
  • Inflammation
  • Macrophages
  • Monocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Caso, R., Silvera, R., Carrio, R., Iragavarapu-Charyulu, V., Gonzalez-Perez, R. R., & Torroella-Kouri, M. (2010). Blood monocytes from mammary tumor-bearing mice: Early targets of tumor-induced immune suppression? International Journal of Oncology, 37(4), 891-900. https://doi.org/10.3892/ijo-00000740

Blood monocytes from mammary tumor-bearing mice : Early targets of tumor-induced immune suppression? / Caso, Raul; Silvera, Risset; Carrio, Roberto; Iragavarapu-Charyulu, Viyaya; Gonzalez-Perez, Ruben R.; Torroella-Kouri, Marta.

In: International Journal of Oncology, Vol. 37, No. 4, 01.10.2010, p. 891-900.

Research output: Contribution to journalArticle

Caso, R, Silvera, R, Carrio, R, Iragavarapu-Charyulu, V, Gonzalez-Perez, RR & Torroella-Kouri, M 2010, 'Blood monocytes from mammary tumor-bearing mice: Early targets of tumor-induced immune suppression?', International Journal of Oncology, vol. 37, no. 4, pp. 891-900. https://doi.org/10.3892/ijo-00000740
Caso R, Silvera R, Carrio R, Iragavarapu-Charyulu V, Gonzalez-Perez RR, Torroella-Kouri M. Blood monocytes from mammary tumor-bearing mice: Early targets of tumor-induced immune suppression? International Journal of Oncology. 2010 Oct 1;37(4):891-900. https://doi.org/10.3892/ijo-00000740
Caso, Raul ; Silvera, Risset ; Carrio, Roberto ; Iragavarapu-Charyulu, Viyaya ; Gonzalez-Perez, Ruben R. ; Torroella-Kouri, Marta. / Blood monocytes from mammary tumor-bearing mice : Early targets of tumor-induced immune suppression?. In: International Journal of Oncology. 2010 ; Vol. 37, No. 4. pp. 891-900.
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