Cell Motility, Adhesion, Homing, and Migration Assays in the Studies of Tyrosine Kinases

The malignant potential of many cancers is characterized by the rate of metastsis. Metastasis is a multistep process that in general requires detachment from the original tissue, migration through the vascular endothelium, circulation in the blood, attachment to the inner blood vessel wall and penetration into surrounding tissue (1 ). For example, lung cancer cells have a very high rate of metastasis with cells invading virtually every organ in the body with a predilection to brain, bone, bone marrow, liver and adrenal glands. There are intrinsic abnormalities of cell motility of these lung cancer cells with increased propensity to invade and metastasize to the other organs (2 ). Most of the cell motility processes are tightly regulated by tyrosine kinases (3 ) and protein tyrosine phosphatases (4 ). In malignant cells, these crucial pathways can be brought out of balance through constitutive activation of growth factor receptors and their associated kinases or through formation of tyrosine kinase oncogenes. Overexpression and activation of receptor tyrosine kinases (RTKs) has been found in non small cell lung cancer (NSCLC) cells, including epidermal growth factor receptor (EGFR), HER2/neu, c-Met, and in small cell lung cancer (SCLC) cells, including c-Kit and c-Met receptors (5 ). The downstream targets of these kinases can involve cytoskeletal proteins which are important in cell motility, cell migration and invasion. It is also known that the tyrosine kinase oncogene BCR/ABL, the transforming protein in chronic myeloid leukemia (CML), is a potent kinase for inducing increased cell motility (membrane ruffling, filipodia formation, lamellopodia formation, and formation of uropod) and migration over extracellular matrix components such as fibronectin (6 ).