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

• Published in: FEBS letters Vol. 563; no. 1; pp. 98 - 102
• Main Authors: Hellmuth, Markus, Paulukat, Jens, Ninic, Raiko, Pfeilschifter, Josef, Mühl, Heiko
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 09.04.2004
• Subjects: Angiogenesis; Biomarkers; Carcinoma - genetics; Carcinoma - pathology; Cell Line, Tumor; Chemokine; Colon carcinoma cell; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Enzyme-Linked Immunosorbent Assay; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Gene Expression Regulation, Neoplastic - physiology; Humans; IFNγ, interferon-γ; IL, interleukin; iNOS, inducible nitric oxide synthase; Interferon-gamma - metabolism; Interleukin-1 - metabolism; Interleukin-10 - metabolism; Interleukin-8 - metabolism; IP-10, interferon-inducible protein-10; MIG, monokine induced by interferon-γ; Neovascularization, Pathologic - genetics; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - genetics; NO, nitric oxide; RNA, Messenger - metabolism; Vascular Endothelial Growth Factor A - metabolism; VEGF, vascular endothelial growth factor; Chemokine; Angiogenesis; IP-10, interferon-inducible protein-10; MIG, monokine induced by interferon-γ; NO, nitric oxide; Nitric oxide; IL, interleukin; IFNγ, interferon-γ; iNOS, inducible nitric oxide synthase; VEGF, vascular endothelial growth factor; Colon carcinoma cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(04)00275-3

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-γ (MIG). These chemokines are expressed by DLD-1 colon carcinoma cells after stimulation with IL-1β/interferon-γ. 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.