Fibronectin in malignancy - Effect of aging

Fibronectin (Fn) was the first 'structural' glycoprotein intensively studied as an ubiquitous matrix component of early phylogenetic appearance, Its age-dependent increase in plasma and tissues may be accompanied in Pathological states, especially in tumor growth, by its proteolytic breakdown by a number of neutral Proteases. It was also shown that several of its proteolytic breakdown products exhibit unexpected and mostly harmful biological activities. The first of these effects was a potentiation of malignant transformation. Some fragments had proteolytic activity, others behaved as proinflammatory agents stimulating IL-1 and collagenolytic MMP up-regulation. This matricryptic potential of Fn was followed by several other examples of proteolytic Production of biologically active peptides. The study of solid human tumors showed among the early signs of malignant transformation the fragmentation of pericellular Fn, concommitent with the increase of its production by the peritumoral stroma. These results should encourage further investigations concerning the potential importance of Fn production and breakdown during cancer progression.