MOTILITY OF FIBRONECTIN RECEPTOR-DEFICIENT CELLS ON FIBRONECTIN AND VITRONECTIN - COLLABORATIVE INTERACTIONS AMONG INTEGRINS

Cells are capable of adhering to and migrating on protein components of the extracellular matrix. These cell-matrix interactions are thought to be mediated largely through a family of cell surface receptors termed integrins. However, the manner in which individual integrins are involved in cell adhesion and motility has not been fully determined. To explore this issue, we previously selected a series of CHO variants that are deficient in expression of the integrin alpha-5-beta-1, the "classical" fibronectin receptor. Two sets of subclones of these variants were defined which respectively express approximately 20% or 2% of fibronectin receptor on the cell surface when compared to wild-type cells (Schreiner, C. L., J. S. Bauer, Y. N. Danilov, S. Hussein, M. M. Sczekan, and R. L. Juliano. 1989. J Cell Biol. 109:3157-3167). In the current study, the variant clones were tested for haptotactic motility on substrata coated with fibronectin or vitronectin. Data from assays using fibronectin show that cellular motility of the 20% variants was substantially decreased (30-75 % of wild type), while the motility of the 2% variants was nearly abolished (2-20% of wild type). Surprisingly, a similar pattern was seen for haptotactic motility of both 2% and 20% variants when vitronectin was used (almost-equal-to 20- 30% of wild type). The reduced haptotactic motility of the fibronectin receptor-deficient variant clones on vitronectin was shown not to be due to reduced vitronectin receptor (alpha-v-beta-3) expression nor to a failure of these variants to adhere to vitronectin substrata. Transfection of the deficient variants with a cDNA for the human alpha-5 subunit resulted in normal levels of fibronectin receptor expression (as a human alpha-5/hamster beta-1 chimera) and restored the motility of the CHO variants on fibronectin and vitronectin. This indicates that expression of the alpha-5 subunit is required for normal haptotactic motility on vitronectin substrata and suggests that the fibronectin receptor (alpha-5-beta-1) plays a cooperative role with vitronectin receptors in cell motility.