Macrophage inflammatory protein inhibition may curb myeloma bone destruction

By Megan Rauscher

NEW YORK (Reuters Health) – Blocking macrophage inflammatory protein 1-alpha (MIP-1alpha) production by a human myeloma cell line decreases both tumor burden and bone destruction in a mouse model of human multiple myeloma.

Dr. G. David Roodman, of the University of Pittsburgh Cancer Institute, and associates report the finding in the December 2001 issue of The Journal of Clinical Investigation.

MIP-1alpha is a recently identified osteoclast-activating factor produced by myeloma cells. "Approximately 60% to 70% of myeloma patients have increased levels of MIP-1alpha in their marrow, and increased MIP-1alpha levels correlate with disease activity and have been associated with a poor prognosis," Dr. Roodman told Reuters Health.

His team transfected a human multiple myeloma cell line with an antisense construct of MIP-1alpha or an empty control vector and then transplanted these cells into SCID mice.

MIP-1alpha levels in marrow plasma were significantly decreased in mice receiving the antisense MIP-1alpha construct compared with those receiving empty vector, the team reports. Adhesive interactions between myeloma cells and marrow stromal cells were also decreased in actively treated animals.

Mice that received the antisense MIP-1alpha construct lived longer than control mice and, unlike controls, had no radiologic evidence of lytic lesions. They also had reduced tumor burden and fewer osteoclasts per square millimeter of bone and bone surface.

"These data support an important role for MIP-1alpha in cell homing, survival, and bone destruction in multiple myeloma," Dr. Roodman and colleagues write in their report.

"Our [study] suggests that blocking the effects of MIP-1alpha, either by inhibiting its production or blocking MIP-1alpha binding to its receptor, may have a beneficial therapeutic effect in patients with myeloma," Dr. Roodman told Reuters Health.

J Clin Invest 2001;108:1833-1841.

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