Nitric oxide differentially regulates pro- and anti-angiogenic markers in DLD-1 colon carcinoma cells

FEBS Lett. 2004 Apr 9;563(1-3):98-102. doi: 10.1016/S0014-5793(04)00275-3.

Abstract

Inducible nitric oxide (NO) synthase (iNOS) appears to be a marker of tumor progression in colon carcinogenesis. Here we investigated effects of NO on selected chemokines that differentially regulate angiogenesis, namely pro-angiogenic interleukin (IL)-8 as well as tumor-suppressive interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG). These chemokines are expressed by DLD-1 colon carcinoma cells after stimulation with IL-1beta/interferon-gamma. Expression of IL-8 was markedly upregulated by NO. Moreover, NO enhanced expression of vascular endothelial growth factor (VEGF). In contrast, expression of IP-10 and MIG was suppressed by NO. The present data are consistent with previous observations that link NO to enhanced tumor angiogenesis and imply that NO-mediated upregulation of IL-8 and VEGF as well as downregulation of IP-10 and MIG may contribute to this phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-8 / metabolism
  • Neovascularization, Pathologic / genetics*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / genetics
  • RNA, Messenger / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase