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Roles of nitric oxide in tumor growth
D C Jenkins1, I G Charles, L L Thomsen
1Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Abstract:
A subclone of the human colon adenocarcinoma cell line DLD-1, which grew reproducibly as subcutaneous tumors in nude mice, was isolated. Such cells, when engineered to generate nitric oxide (NO) continuously, grew more slowly in vitro than the wild-type parental cells. This growth retardation was reversed by the addition of N-iminoethyl-L-ornithine. In nude mice, however, the tumors from these cells grew faster than those derived from wild-type cells and were markedly more vascularized, suggesting that NO may act as part of a signaling cascade for neovascularization. Recent observations that the generation of NO in human breast and gynecological cancers correlates positively with tumor grade are consistent with this hypothesis. We suggest that NO may have a dual pro- and antitumor action, depending on the local concentration of the molecule.
Insights
Nitric oxide (NO) slowed colon cancer cell growth in vitro but accelerated tumor growth and vascularization in mice. This suggests NO has a dual role in cancer, potentially promoting or inhibiting tumors based on concentration.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Nitric oxide (NO) is a signaling molecule implicated in various physiological and pathological processes, including cancer.
- The precise role of NO in tumor growth and progression remains complex and context-dependent.
Purpose of the Study:
- To investigate the effect of continuous nitric oxide (NO) generation on the growth and vascularization of human colon adenocarcinoma cells (DLD-1) in vitro and in vivo.
- To explore the potential role of NO in tumor neovascularization.
Main Methods:
- Isolation of a DLD-1 subclone that forms reproducible subcutaneous tumors in nude mice.
- Engineering cells to continuously generate nitric oxide (NO).
- Assessment of cell growth in vitro and tumor growth and vascularization in vivo in nude mice.
Main Results:
- Cells engineered to produce NO exhibited slower growth in vitro, an effect reversed by N-iminoethyl-L-ornithine.
- In vivo, tumors derived from NO-producing cells grew faster and showed increased vascularization compared to wild-type tumors.
- These findings align with observations of NO generation correlating positively with tumor grade in human breast and gynecological cancers.
Conclusions:
- Nitric oxide (NO) exhibits a dual role in cancer, potentially inhibiting tumor cell proliferation in vitro while promoting tumor growth and neovascularization in vivo.
- NO may act as a signaling molecule in the neovascularization cascade, contributing to increased tumor vascularity.
- Local concentration of NO is likely a critical determinant of its pro- or antitumorigenic effects in different cancer contexts.