Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor.
The 67 kD laminin receptor (67LR) binds laminin-1 (LN), major component of the basement membrane, with high affinity. In this study, we demonstrated that human multiple myeloma cell lines (HMCL) and murine 5T2MM cells express 67LR. CD38(bright+) plasma cells in fresh multiple myeloma (MM) bone marrow (BM) samples showed weaker 67LR expression, but expression increased after direct exposure to a BM endothelial cell line (4LHBMEC). LN stimulated the in vitro migration of 3 HMCL (MM5.1, U266 and MMS.1), primary MM cells and the murine 5T2MM cells. 67LR has been shown to mediate the actions of LN through binding to CDPGYIGSR, a 9 amino acid sequence from the B1 chain of LN. MM cell migration was partially blocked by peptide 11, a synthetic nonapeptide derived from this amino sequence and also by a blocking antiserum against 67LR. Co-injection of peptide 11 with 5T2MM cells in a murine in vivo model of MM resulted in a decreased homing of 5T2MM cells to the BM compartment. In conclusion, LN acts as a chemoattractant for MM cells by interaction with 67LR. This interaction might be important during extravasation of circulating MM cells.
Vande Broek
I
I
Department of Hematology and Immunology, Free University Brussels, Laarbeeklaan 101, Brussels, B-1090, Belgium.
Vanderkerken
K
K
De Greef
C
C
Asosingh
K
K
Straetmans
N
N
Van Camp
B
B
Van Riet
I
I
D000818:Animals; D001854:Bone Marrow Cells; D002465:Cell Movement; D002630:Chemotactic Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology*; D009360:Neoplastic Cells, Circulating; D017474:Receptors, Laminin / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002630:Chemotactic Factors; D007797:Laminin; D017474:Receptors, Laminin; C121346:laminin 1