title: Tumor invasion and host extracellular matrix.
abstract: In this review some of the major mechanistic pathways by which tumor cells are thought to invade host tissues are discussed. Tumor invasion has been conceived to be the result of pathological, close-range interactions between malignant cells and host stroma. The sequence of events that characterize invasion can be summarized as follows: (a) Tumor cell clusters break from the confinement of the primary tumor. Loss of intercellular junctions (desmosomes), alterations in the chemical composition and physical properties of the cell surface coat (loss of fibronectin and heparan sulfate; excessive amounts of hyaluronate), and loosening of cell-substrate interactions (loss of hemidesmosomes, fibronectin, and heparan sulfate), are among the most frequently listed causes of tumor cell shedding. (b) Increased proteolytic activities at the invasion front cause focal alterations in the surrounding extracellular matrix, thereby changing its physical properties. Collagenases and cathepsins, as well as elastase and other neutral proteinases are the enzymes most frequently associated with matrix destruction and invasion. In some tissues this process is effectively regulated by inhibitors of matrix-degrading, proteolytic enzymes. (c) Tumor cells migrate into the altered matrix, possibly moving as aggregates along guidance tracks provided by host structures (blood vessels, lymphatics, nerves) or matrix macromolecules (collagen and fibronectin tracks). Migration seems to be preceded by increased swelling of glycosaminoglycan (i.e., hyaluronate) in the matrix, ahead of the migrating cell population. Various host cell types (mast cells, fibroblasts, endothelial cells, macrophages, etc.) may participate in these events.
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D002633:Chemotaxis; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005110:Extracellular Space / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D005353:Fibronectins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D003094:Collagen; D004549:Elastin; D010447:Peptide Hydrolases