Mechanisms of nitric oxide-dependent regulation of tumor invasion and metastasis

Aideen E. Ryan, Amy J. Burke, Francis J. Giles, Francis J. Sullivan, Sharon A. Glynn*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations


The nitric oxide synthases (NOS) are key enzymes activated as part of the wound healing and host immune response. Their product nitric oxide (NO) is a short-lived, pleiotropic molecule that is a key physiological signaling molecule. Emerging evidence suggests that the NOS may be key regulators of tumor invasion and metastasis. However, there are markedly conflicting findings in the literature regarding NO and its role in carcinogenesis and tumor progression, and in particular its effect on tumor invasion and metastasis. In this review, we present the evidence for the roles played by the NOS in particular focusing on their cellular sources, which include but are not limited to tumor epithelial cells and tumor-associated macrophages. We propose that NOS expression in tumor epithelia cells tends towards activation of tumor-promoting effects, while NOS expression in tumor-associated macrophages has a tumor-inhibitory effect. The balance between the two as such determines whether a tumor progresses or regresses. This presents a therapeutic opportunity to target tumor invasion and metastasis by either disrupting tumor epithelial NOS expression by NOS inhibition, or by introducing NOS vectors or NO-donating drugs to increase the levels of intratumor NO to those that induce DNA damage and apoptosis.

Original languageEnglish (US)
Title of host publicationNitric Oxide and Cancer
Subtitle of host publicationPathogenesis and Therapy
PublisherSpringer International Publishing
Number of pages16
ISBN (Electronic)9783319136110
ISBN (Print)9783319136103
StatePublished - Jan 1 2015


  • Immune infiltration
  • Metastasis
  • Nitric oxide
  • Pro- & anti-tumour immune responses
  • Tumour associated macrophages

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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