Antisense inhibition of macrophage inflammatory protein 1-α blocks bone destruction in a model of myeloma bone disease

摘要: We recently identified macrophage inflammatory protein 1-α (MIP-1α) as a factor produced by multiple myeloma (MM) cells that may be responsible for the bone destruction in MM (1). To investigate role of MIP-1α disease vivo, human MM–derived cell line ARH was stably transfected with an antisense construct to (AS-ARH) and tested its capacity induce SCID mice. Human levels marrow plasma from AS-ARH mice were markedly decreased compared controls treated empty vector (EV-ARH). Mice lived longer than and, unlike controls, they showed no radiologically identifiable lytic lesions. Histomorphometric analysis demonstrated osteoclasts (OCLs) per square millimeter OCLs surface significantly less EV-ARH mice, percentage tumors total area also decreased. adherence stromal cells, due reduced expression α5β1 integrin diminished homing survival. These data support important homing, survival, MM.