Chemokine receptors and chemokine production by CD34+ stem cell-derived monocytes in response to cancer cells

Anticancer Res. 2012 Nov;32(11):4749-53.

Abstract

Background: The chemokine-chemokine receptor (CR) network is involved in the regulation of cellular infiltration of tumours. Cancer cells and infiltrating macrophages produce a whole range of chemokines. This study explored the expression of some CR and chemokine production by cord blood stem cell-derived CD34(+) monocytes and their novel CD14(++)CD16(+) and CD14(+)CD16(-) subsets in response to tumour cells.

Material and methods: CR expression was determined by flow cytometry and their functional activity by migration to chemoattractants. Monocytes were cultured with tumour cells and the chemokine content was assessed in culture supernatants.

Results: CD14(++)CD16(+) monocytes exhibited increased expression of chemokine (C-C) receptor (CCR) 1, while CD14(+)CD16(-) of CCR2, chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on CD14(+)CD16(-) monocytes was associated with their enhanced migration to monocyte chemoattractant protein-1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13), while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell-derived factor-1 (CXCL12). Tumour cells induced production of macrophage inflammatory protein-1α (CCL3) MIP-1β and regulated on activation normal T-cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10).

Conclusion: The studied monocyte subsets, in comparison to those from blood, exhibit different expression of CRs and response to the stimuli that occur from tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism*
  • Cell Communication / immunology
  • Cell Line, Tumor
  • Chemokines / biosynthesis*
  • Chemotaxis, Leukocyte / immunology
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Fetal Blood / metabolism
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Neoplasms / immunology*
  • Receptors, Chemokine / metabolism*
  • Tumor Microenvironment / immunology

Substances

  • Antigens, CD34
  • Chemokines
  • Receptors, Chemokine