Paracrine regulation of vascular endothelial growth factor-A expression during macrophage-melanoma cell interaction

Role of monocyte chemotactic protein-1 and macrophage colony-stimulating factor

Michelle L. Varney, Kimberlee J. Olsen, R Lee Mosley, Rakesh K Singh

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Tumor-associated macrophages are major infiltrates of human solid malignancies and play an important role in tumor angiogenesis by production of angiogenic factors. In the present study, we examined whether macrophage-melanoma cell interaction regulates vascular endothelial cell growth factor-A (VEGF-A) expression in macrophages. We analyzed the expression of mediators of monocyte recruitment and differentiation, such as monocyte chemotactic protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) in malignant melanoma specimens and tumor cells with different metastatic potential. Our data demonstrate that MCP-1 and M-CSF are differentially expressed in human malignant melanomas from different thickness and depth of invasion and cell lines. Next, we examined the effect of MCP-1 and M-CSF on modulation of VEGF-A expression in monocytes/macrophages. Treatment of human monocytes with M-CSF and MCP-1 enhanced VEGF-A expression by increased hypoxia-inducible factor-1α (HIF-1α) expression and enhanced activation of the hypoxia response element (HRE). Further activation of monocytes and monocyte-derived macrophages (MDM) by lipopolysaccharide (LPS) caused an increase in VEGF-A expression. We demonstrate that coculture of melanoma cells with monocytes enhanced VEGF-A secretion, and conditioned medium from MDMs enhanced melanoma cell expression of VEGF-A. Furthermore, conditioned medium from melanoma cells enhanced VEGF-A expression in human monocytes, which was abrogated by anti-M-CSF neutralizing antibody. In summary, we demonstrate that MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage-mediated tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)674-683
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2005

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Macrophage Colony-Stimulating Factor
Chemokine CCL2
Cell Communication
Vascular Endothelial Growth Factor A
Monocytes
Melanoma
Macrophages
Neoplasms
Conditioned Culture Medium
Hypoxia-Inducible Factor 1
Angiogenesis Inducing Agents
Response Elements
Coculture Techniques
Neutralizing Antibodies
Lipopolysaccharides
Cell Line

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

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title = "Paracrine regulation of vascular endothelial growth factor-A expression during macrophage-melanoma cell interaction: Role of monocyte chemotactic protein-1 and macrophage colony-stimulating factor",
abstract = "Tumor-associated macrophages are major infiltrates of human solid malignancies and play an important role in tumor angiogenesis by production of angiogenic factors. In the present study, we examined whether macrophage-melanoma cell interaction regulates vascular endothelial cell growth factor-A (VEGF-A) expression in macrophages. We analyzed the expression of mediators of monocyte recruitment and differentiation, such as monocyte chemotactic protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) in malignant melanoma specimens and tumor cells with different metastatic potential. Our data demonstrate that MCP-1 and M-CSF are differentially expressed in human malignant melanomas from different thickness and depth of invasion and cell lines. Next, we examined the effect of MCP-1 and M-CSF on modulation of VEGF-A expression in monocytes/macrophages. Treatment of human monocytes with M-CSF and MCP-1 enhanced VEGF-A expression by increased hypoxia-inducible factor-1α (HIF-1α) expression and enhanced activation of the hypoxia response element (HRE). Further activation of monocytes and monocyte-derived macrophages (MDM) by lipopolysaccharide (LPS) caused an increase in VEGF-A expression. We demonstrate that coculture of melanoma cells with monocytes enhanced VEGF-A secretion, and conditioned medium from MDMs enhanced melanoma cell expression of VEGF-A. Furthermore, conditioned medium from melanoma cells enhanced VEGF-A expression in human monocytes, which was abrogated by anti-M-CSF neutralizing antibody. In summary, we demonstrate that MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage-mediated tumor angiogenesis.",
author = "Varney, {Michelle L.} and Olsen, {Kimberlee J.} and Mosley, {R Lee} and Singh, {Rakesh K}",
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T2 - Role of monocyte chemotactic protein-1 and macrophage colony-stimulating factor

AU - Varney, Michelle L.

AU - Olsen, Kimberlee J.

AU - Mosley, R Lee

AU - Singh, Rakesh K

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Tumor-associated macrophages are major infiltrates of human solid malignancies and play an important role in tumor angiogenesis by production of angiogenic factors. In the present study, we examined whether macrophage-melanoma cell interaction regulates vascular endothelial cell growth factor-A (VEGF-A) expression in macrophages. We analyzed the expression of mediators of monocyte recruitment and differentiation, such as monocyte chemotactic protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) in malignant melanoma specimens and tumor cells with different metastatic potential. Our data demonstrate that MCP-1 and M-CSF are differentially expressed in human malignant melanomas from different thickness and depth of invasion and cell lines. Next, we examined the effect of MCP-1 and M-CSF on modulation of VEGF-A expression in monocytes/macrophages. Treatment of human monocytes with M-CSF and MCP-1 enhanced VEGF-A expression by increased hypoxia-inducible factor-1α (HIF-1α) expression and enhanced activation of the hypoxia response element (HRE). Further activation of monocytes and monocyte-derived macrophages (MDM) by lipopolysaccharide (LPS) caused an increase in VEGF-A expression. We demonstrate that coculture of melanoma cells with monocytes enhanced VEGF-A secretion, and conditioned medium from MDMs enhanced melanoma cell expression of VEGF-A. Furthermore, conditioned medium from melanoma cells enhanced VEGF-A expression in human monocytes, which was abrogated by anti-M-CSF neutralizing antibody. In summary, we demonstrate that MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage-mediated tumor angiogenesis.

AB - Tumor-associated macrophages are major infiltrates of human solid malignancies and play an important role in tumor angiogenesis by production of angiogenic factors. In the present study, we examined whether macrophage-melanoma cell interaction regulates vascular endothelial cell growth factor-A (VEGF-A) expression in macrophages. We analyzed the expression of mediators of monocyte recruitment and differentiation, such as monocyte chemotactic protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) in malignant melanoma specimens and tumor cells with different metastatic potential. Our data demonstrate that MCP-1 and M-CSF are differentially expressed in human malignant melanomas from different thickness and depth of invasion and cell lines. Next, we examined the effect of MCP-1 and M-CSF on modulation of VEGF-A expression in monocytes/macrophages. Treatment of human monocytes with M-CSF and MCP-1 enhanced VEGF-A expression by increased hypoxia-inducible factor-1α (HIF-1α) expression and enhanced activation of the hypoxia response element (HRE). Further activation of monocytes and monocyte-derived macrophages (MDM) by lipopolysaccharide (LPS) caused an increase in VEGF-A expression. We demonstrate that coculture of melanoma cells with monocytes enhanced VEGF-A secretion, and conditioned medium from MDMs enhanced melanoma cell expression of VEGF-A. Furthermore, conditioned medium from melanoma cells enhanced VEGF-A expression in human monocytes, which was abrogated by anti-M-CSF neutralizing antibody. In summary, we demonstrate that MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage-mediated tumor angiogenesis.

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