Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas

The majority of cancer researchers have been focusing on tumour cells themselves and investigating their alterations in morphology, biology and function in tumour processes. However, stromal variables within or around tumours, including blood and lymph vessels, stromal cells, and various types of proteins, have not drawn enough attention even though they have important impacts on tumour development and progression. Tumour angiogenesis and lymphangiogenesis are the processes of creating new blood vessels or lymph vessels within and surrounding tumours. Stromal cells consist of various cell types such as infiltrating immune cells, fibroblasts, and endothelial cells. The extracellular matrix (ECM) is a complex structural entity surrounding tumour cells, and is often referred to as the connective tissue or ground substance. The ECM is composed of three major classes of biomolecules; structural proteins (collagen and elastin), specialized proteins (fibrillin, fibronectin, and laminin), and proteoglycans [1,2].A better understanding of the role of stromal variables in tumour development is required for designing appropriate therapeutic strategies against angiogenesis and stromal proteinases. A number of anti-angiogenesis elements and matrix metalloproteinase (MMP) inhibitors (MMPI) have recently been developed, and some have reached clinical trials [3-7]. Compared to tumour cells, stromal variables are more attractive therapeutic targets, due to lower drug resistance and few side effects [8].In this article, we mainly review the clinicopathological significance of stromal variables, including angiogenesis, lymphangiogenesis, inflammatory infiltration, MMPs and the particularly interesting new cysteine-histidine rich protein (PINCH) in colorectal cancer (CRC).In general, normal tissues have a barrier, preventing either endothelial cell migration or tumour cell invasion. The effect of this barrier can be interrupted by newly-formed stroma, namely stromatogenesis, during the