Regulation of cell migration by the integrin β subunit ectodomain

CS-1 melanoma cells transfected with cDNAs encoding either the β3 or β5 integrin subunit protein express αvβ3 or αvβ5, respectively, enabling them to adhere to vitronectin yet only αvβ3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, αvβ5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in β3 or β5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric β subunit proteins, in which the ectoand cytoplasmic domains of β3 and β5 were exchanged (termed αvβ3/5 or αvβ5/3). Surprisingly, αvβ3/5 expressing cells spread and migrate on vitronectin while cells expressing αvβ5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins αvβ3 and αvβ5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin β subunit.