Tumor invasion is a process in which cancer cells or their groups (aggregates) diverge from the primary focus of the tumor into neighboring tissues. In the case of carcinomas , this is a process involving the penetration of tumor cells through the basement membrane as a result of its destruction. As a rule, invasion is the first stage of a complex invasive-metastatic cascade, leading to further metastasis. The main sign of invasion is the breakthrough of the basement membrane and the emergence or growth of tumor cells beyond its limits, allowing them to acquire additional benefits, for example, improved supply of oxygen and nutrients.
Tumor invasion mechanisms
Some tumor cells undergo an epithelial-mesenchymal transition and acquire the phenotype of mesenchymal cells, which have increased mobility, the ability to secrete extracellular matrix components, as well as degrade these components and produce some growth factors. These cells with the help of enzymes - matrix metalloproteinases trigger the degradation of collagen IV, laminins - the components of the basement membrane. Neighboring stromal cells ( fibroblasts , monocytes , lymphocytes , endotheliocytes) secrete many growth factors that contribute to the activation of proteinase gene expression, in addition, these cells enhance the action of tumor cells by activating an important proteolytic plasminogen activation cascade.
The role of the plasminogen activation cascade in tumor invasion .
Tumor stromal cells secrete an urokinase-type plasminogen activator (uPA) in an inactive single-chain form (scuPA), on the surface of the tumor cells they bind to its receptor (uPAR) and are activated by plasmin. The urokinase plasminogen activator is a proteinase that, in its active form, catalyzes the conversion of plasminogen to plasmin , that is, into active proteinase. Next, plasmin activates matrix proteinases by cleaving their inactive pro-enzymes and converting them into active enzymes , which then break down the components of the extracellular matrix .