CHANGES IN THE FIBRONECTIN-SPECIFIC INTEGRIN EXPRESSION PATTERN MODIFY THE MIGRATORY BEHAVIOR OF SARCOMA S180 CELLS IN-VITRO AND IN THE EMBRYONIC ENVIRONMENT

The molecules that mediate cell-matrix recognition, such as fibronecti ns (FN) and integrins, modulate cell behavior. We have previously demo nstrated that FN and the beta 1-integrins are used during neural crest cell (NCC) migration in vitro as well as in vivo, and that the FN cel l-binding domains I and II exhibit functional specificity in controlli ng either NCC attachment, spreading, or motility in vitro. In the pres ent study, we have analyzed the effect of changes in the integrin expr ession patterns on migratory cell behavior in vivo. We have generated, after stable transfection, S180 cells expressing different levels of alpha 4 beta 1 or alpha 5 beta 1 integrins, two integrins that recogni ze distinct FN cell-binding domains. Murine S180 cells were chosen bec ause they behave similarly to NCC after they are grafted into the NCC embryonic pathways in the chicken embryo. Thus, they provide a model s ystem with which to investigate the mechanisms controlling in vitro an d in vivo migratory cell behavior. We have observed that either the ov erexpression of alpha 5 beta 1 integrin or the induction of alpha 4 be ta 1 expression in transfected S180 cells enhances their motility on F N in vitro. These genetically modified S180 cells also exhibit differe nt migratory properties when grafted into the early trunk NCC migrator y pathways. We observe that alpha 5 and low alpha 4 expressors migrate in both the ventral and dorsolateral paths simultaneously, in contras t to the parental S180 cells or the host NCC, which are delayed by 24 h in their invasion of the dorsolateral path. Moreover, the alpha 4 ex pressors exhibit different migratory properties according to their lev el of alpha 4 expression at the cell surface: Cells of the low alpha 4 expressor line invade both the ventral and dorsolateral pathways. In contrast, the high expressors remain as an aggregate at the graft site , possibly the result of alpha 4 beta 1-dependent homotypic aggregatio n. Thus, changes in the repertoire of FN-specific integrins enable the S180 cells to exploit different pathways in the embryo and regulate t he speed with which they disperse in vivo and in culture. Our studies correlate well with known changes in integrin expression during neural crest morphogenesis and strongly suggest that neural crest cells that migrate into the dorsolateral path, i.e., melanoblasts, do so only af ter they have upregulated the expression of FN receptors. Some of our in vivo results are at variance with what was expected, based on the i n vitro behavior of the S180-transfected clones, and they demonstrate the importance of examining cell behavior in the tissue environment.