Insulin-like growth factor-1 acts as a chemoattractant factor for 5T2 multiple myeloma cells

The chemotactic and growth-stimulatory effect of insulinlike growth factor 1 (IGF-1) was investigated in the experimental mouse 5T2 multiple myeloma ( MM) model. Chemotaxis was analyzed by classical checkerboard analysis. Bone marrow fibroblasts-conditioned medium exhibited a chemotactic effect on 5T 2 MM cells that could be neutralized by adding a blocking antibody to IGF-1 . On the other hand, exogenously added IGF-1 also had a chemotactic effect on the 5T2 MM cells. Moreover, in vitro analysis demonstrated that transmig rated 5T2 MM cells have a higher expression of IGF-1 receptor, both in bone marrow-conditioned medium and in IGF-1-induced chemotaxis, in comparison t o cells before migration. When analyzed in vivo, 18 hours after injection o f the heterogeneous 5T2 MM population, 5T2 MM cells present in the bone mar row show a higher expression of the IGF-1 receptor than their counterparts before injection. When the proliferative effect of IGF-1 was analyzed, no s timulation was observed, which is in contrast to the influence of bone marr ow-conditioned medium and interleukin-6. Our results suggest a causal relat ionship between the presence of IGF-1 in the bone marrow and the chemotaxis of MM cells to and their subsequent presence in the bone marrow. (C) 1999 by The American Society of Hematology.