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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 235-241
Insulin-Like Growth Factor-1 Acts as a Chemoattractant Factor for
5T2 Multiple Myeloma Cells
Karin Vanderkerken,
Kewal Asosingh,
Filip Braet,
Ivan Van Riet, and
Ben Van Camp
From the Departments of Hematology and Immunology (HEIM)
and Cell Biology (CYTO), Free University Brussels, Brussels, Belgium.
The chemotactic and growth-stimulatory effect of insulin-like 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 5T2 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 transmigrated 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 to cells before migration. When analyzed in vivo, 18 hours
after injection of the heterogeneous 5T2 MM population, 5T2 MM cells
present in the bone marrow show a higher expression of the IGF-1
receptor than their counterparts before injection. When the
proliferative effect of IGF-1 was analyzed, no stimulation was
observed, which is in contrast to the influence of bone
marrow-conditioned medium and interleukin-6. Our results suggest a
causal relationship 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.
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