XXXX osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and @entity5 neovasculature.

@entity1 @entity11132 @entity137 @entity263 @entity5 @entity19 @entity3 @entity1611 @entity1865
PURPOSE: A hallmark of @entity263 ( @entity263 ) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that @entity1611 (121)/rGel targets osteoclast precursors and @entity5 neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit @entity5 progression in a clinically relevant model of osteoblastic @entity263 . EXPERIMENTAL DESIGN: Cells from @entity1865 @entity263 118b, a @entity263 xenograft obtained from a bone @entity3 in a @entity1 with castrate-resistant @entity263 , were injected into the femurs of @entity19 . Osteoblastic progression was monitored following systemic administration of @entity1611 (121)/rGel. RESULTS: @entity1611 (121)/rGel was cytotoxic in vitro to osteoblast precursor cells. This @entity137 was specific as @entity1611 (121)/rGel internalization into osteoblasts was @entity1611 (121) receptor driven. Furthermore, @entity1611 (121)/rGel significantly inhibited @entity263 -induced bone formation in a @entity19 calvaria culture assay. In vivo, @entity1611 (121)/rGel significantly inhibited the osteoblastic progression of @entity263 cells in the femurs of @entity19 . Microcomputed tomographic analysis revealed that @entity1611 (121)/rGel restored the bone volume fraction of @entity5 -bearing femurs to values similar to those of the contralateral (non- @entity5 -bearing) femurs. @entity1611 (121)/rGel significantly reduced the number of @entity5 -associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, @entity1611 (121)/rGel-treated @entity19 had significantly less @entity5 burden than control @entity19 . Our results thus indicate that @entity1611 (121)/rGel inhibits osteoblastic @entity5 progression by targeting angiogenesis, osteoclastogenesis, and bone formation. CONCLUSIONS: Targeting @entity1611 receptor (VEGFR)-1- or @entity11132 -expressing cells is effective in controlling the osteoblastic progression of @entity263 in bone. These findings provide the basis for an effective multitargeted approach for metastatic @entity263 .
