Regulation of macrophage production of vascular endothelial growth factor (VEGF) by hypoxia and transforming growth factor β-1
JH Harmey, E Dimitriadis, E Kay, HP Redmond… - Annals of surgical …, 1998 - Springer
JH Harmey, E Dimitriadis, E Kay, HP Redmond, D Bouchier-Hayes
Annals of surgical oncology, 1998•SpringerBackground: Breast tumors contain high numbers of infiltrating macrophages. The role and
function of these cells within the tumor remain unclear, but a number of studies have found
an association between poor prognosis and macrophage content in human breast cancer.
Both hypoxia and TGFβ-1 have been shown to regulate VEGF in other cell types. We
hypothesized that breast tumor-associated macrophages produce VEGF and that
macrophage production of this factor is regulated by both hypoxia and TGFβ-1. Methods …
function of these cells within the tumor remain unclear, but a number of studies have found
an association between poor prognosis and macrophage content in human breast cancer.
Both hypoxia and TGFβ-1 have been shown to regulate VEGF in other cell types. We
hypothesized that breast tumor-associated macrophages produce VEGF and that
macrophage production of this factor is regulated by both hypoxia and TGFβ-1. Methods …
Abstract
Background: Breast tumors contain high numbers of infiltrating macrophages. The role and function of these cells within the tumor remain unclear, but a number of studies have found an association between poor prognosis and macrophage content in human breast cancer. Both hypoxia and TGFβ-1 have been shown to regulate VEGF in other cell types. We hypothesized that breast tumor-associated macrophages produce VEGF and that macrophage production of this factor is regulated by both hypoxia and TGFβ-1.
Methods: Paraffin-embedded breast tumor sections were stained immunohistochemically with anti-VEGF, anti-CD68, and anti-cytokeratin. Monocytes were matured for 3 days in 20% autologous plasma and activated with 1000 U/mL interferon-γ for 24 hours. Supernatants were assayed for VEGF protein by ELISA. Total RNA was isolated from cells and reverse transcribed to cDNA, which was used as a template in PCR reactions for VEGF and β-actin.
Results: Both tumor cells and tumor macrophages produce VEGF in human breast tumors. Hypoxia increases VEGF protein and mRNA levels in monocyte-derived macrophages, whereas TGFβ-1 increases VEGF protein but not mRNA under hypoxic growth conditions.
Conclusions: Breast tumor-associated macrophages may contribute to the angiogenic activity of human breast tumors by producing VEGF. Macrophage production of VEGF is upregulated by hypoxia and TGFβ-1, both of which occur in the tumor environment. Macrophage production of VEGF is regulated at both the mRNA and protein levels.
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