THE L1 ADHESION MOLECULE SUPPORTS ALPHA-V-BETA-3-MEDIATED MIGRATION OF HUMAN TUMOR-CELLS AND ACTIVATED T-LYMPHOCYTES

The L1 adhesion molecule is a member of the immunoglobulin superfamily which is expressed by neural and hematopoietic cells. L1 is primarily a cell surface molecule but in its released form it becomes embedded in the extracellular matrix. In addition to the established L1-L1 homo typic interaction, L1 can bind to alpha v beta 3 in the human. The 6th Ig-like domain is critical for this function. We now demonstrate that a fusion protein containing the 6th Ig-like domain of L1 (6.L1-Fc) ca n support the migration of human MED-B1 (alpha v beta 3(+)) but not of Nalm-6 cells (alpha 5 beta 1(+)). The migration was blocked in the pr esence of a mab to alpha v beta 3 and was not seen on a 6.L1-Fc in whi ch the RGD site was mutated. Activation of human T lymphocytes in the presence of PHA and PMA led to the induction of alpha v beta 3 and alp ha v beta 5 expression and concomitantly induced migration of the cell s on 6.L1-Fc. The migration was blocked by mabs to alpha v beta 3 but not to alpha v beta 5. Our results suggest that L1 exposed at the cell surface or as a matrix constituent can serve as a potent substrate fo r alpha v beta 3 mediated cell migration. (C) 1997 Academic Press.