Composition of tumour tissue and how NO is generated and interacts with its constituents.
The tissue consists mainly of cancer cells, tumour-associated macrophages, cancer-associated fibroblasts, and endothelial cells lining the blood vessels through which these cells get their nutrients, and the tumour cells can metastasize. Nitric oxide (NO) is produced from these cells via different isoforms of NO synthase and works as a signalling molecule for activating various transduction pathways. The extracellular matrix (ECM) of tumour tissue is produced by the resident cells and generally consists of three main categories of proteins: (1) structural proteins: such as collagen, fibronectin, hyaluronan, laminin and elastin; (2) matricellular proteins: such as thrombospondin, osteopontin, periostin and SPARC proteins; (3) MMPs and tissue inhibitors of metalloproteinases (TIMPs). There are mutual interactions between NO, the ECM components and cells for modulating the tumour growth, angiogenesis and metastasis.