Abstract
The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in healthy tissue along with disorganized architecture and irregular behaviour of the residing cells. Nitric oxide (NO) as a pleiotropic molecule exerts different effects on the components of the ECM driving or inhibiting augmented angiogenesis and tumour progression and tumour cell proliferation and metastasis. These effects rely on the concentration of NO within the tumour tissue, the nature of the surrounding microenvironment and the sensitivity of resident cells to NO. In this review article, we summarize the recent findings on the correlation between the levels of NO and the ECM components towards the modulation of tumour angiogenesis in different types of cancers. These are discussed principally in the context of how NO modulates the expression of ECM proteins resulting in either the promotion or inhibition of tumour growth via tumour angiogenesis. Furthermore, the regulatory effects of individual ECM components on the expression of the NO synthase enzymes and NO production were reviewed. These findings support the current efforts for developing effective therapeutics for cancers.
Highlights
Nitric oxide (NO) exerts multiple effects on tumour biology, where it can be both pro- and antitumorigenic depending on the NO dose and duration of exposure
NO is mainly synthesized in the tumour tissue via three nitric oxide synthase (NOS) enzymes: endothelial NOS, inducible NOS and neuronal NOS, all of which can play a role in tumorigenesis including tumour proliferation, angiogenesis and tumour metastasis (Figure 1)
In spite of the recent progress in studying the effects of the mechanical properties of the extracellular matrix (ECM) on NO production in different diseases, limited progress has been achieved in addressing its specific role in cancer metastasis
Summary
Nitric oxide (NO) exerts multiple effects on tumour biology, where it can be both pro- and antitumorigenic depending on the NO dose and duration of exposure. The treatment of bovine aortic endothelial cells (BAECs) with NO donor DEA-NONOate caused enhanced mRNA expression via the cGMP pathway and proteolytic cleavage of pro-MMP-13, further implicating a role for NO in angiogenesis [52].
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