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 homotypic 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) can 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 presence of a mab to alpha v beta 3 and was not seen on a 6.L1-Fc in which 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 alpha v beta 5 expression and concomitantly induced migration of the cells 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 for alpha v beta 3 mediated cell migration.
Duczmal
A
A
Tumor Immunology Programme, German Cancer Research Center, Heidelberg, Germany.
Schöllhammer
S
S
Katich
S
S
Ebeling
O
O
Schwartz-Albiez
R
R
Altevogt
P
P
D002465:Cell Movement; D006801:Humans; D039841:Leukocyte L1 Antigen Complex; D008213:Lymphocyte Activation; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D014407:Tumor Cells, Cultured
D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D019030:Receptors, Vitronectin