Invasion and metastasis of tumorInvasion and metastasis are biological hallmarks of malignant tumors. This involve a series of steps -​Detachment of tumor cellsDetachment of tumor cells is the first step in metastasis. Normally cells are glued to each other by adhesion molecules E-cadherin. Normal function of E-cadherin is dependent on catenins that helps in linkage of cytoskeleton to E-cadherin. Down regulation of expression of either E-cadherins or catenins results loosening of cells that helps in metastasis. Attachment to ECM (including basement membrane)Tumor cells express integrins that helps in the attachement of cells to many components of ECM like fibronectin, laminin, vitronectin, and collegen.Degradation of ECMAfter attachement to ECM components, tumor cells must create passageways for migration. This require enzymatic degradation of ECM. Tumor cells secrete proteolytic enzymes themselves or stimulate macrophages and fibroblasts to secrete these enzymes. The most important proteases are metalloproteinases (MMPs) including collagenase IV.Vascular dissemination and homing of tumor cellsAfter travelling through ECM, tumor cells enter into the vessels. In the vessels, tumor cells tend to aggregate in clumps. This is due to adhesion between tumor cells and blood cells, particularly platelets. This clump is carried away at distant site where it adhere to endothelium, followed by extravasation from the vessels. Adhesion to endothelium and further travelling through ECM require same mechanism, as was required initially for attachement and degradation of ECM. At new site, tumor cells proliferate and develops new blood supply → metastatic secondary tumor mass. Note → Among adhesion molecule CD44 is of particular interest, which is expressed on normal T-cells and is used by these cells to migrate to selective sites in lymphoid tissue.Also knowEzrin is the only metastatis gene, that has been identified till now. It is necessary for metastasis of rhabdomyosarcoma and osteosarcoma. In contrast, several antimetastasis gene have been recognized. The important ones are → NM 23, KAI - 1, Kiss gene.