Bone sialoprotein (BSP) and osteopontin ( @entity1096 ) are important factors in the @entity3 of @entity0 , which were examined as targets for antineoplastic therapy by siRNA. In addition, the effect of gene silencing on their transcription factor @entity8087 and their interaction partners integrin b(3) and @entity1476 was studied. The effect of siRNAs directed against these genes was assessed by monitoring expression levels followed by functional assays in cell culture as well as skeletal metastases caused by @entity1 MDA-MB-231(luc) @entity0 cells in nude @entity35 . Upon silencing of the targets, cell migration was profoundly impaired (p < 0.001 for BSP-siRNA), but the impact on proliferation was low. Systemic administration by osmotic mini-pumps of BSP-siRNA but not @entity1096 -siRNA decreased osteolytic lesions (p = 0.067). @entity5 growth was not affected. As an alternative approach, non-viral, polymeric based formulations of siRNAs in nanoparticles (NP) were developed. Locoregional administration of the two siRNAs targeting @entity1096 and BSP encapsulated in these biodegradable NP @entity75 even more efficiently (p = 0.03). Compared to systemic administration, this treatment caused not only a more pronounced anti-osteolytic effect at a 25-fold lower total siRNA dose, but also had a slight reducing effect on @entity5 incidence (p = 0.095). In conclusion, the siRNA treatment had a small effect on cellular proliferation but a significant efficacy against migration of and @entity3061 induced by MDA-MB-231 cells. Our data underline that siRNA mediated knockdown is a powerful tool for identifying targets for pharmacological intervention. In addition, encapsulation of siRNA into biodegradable NP is a strategy, which promises well for using siRNA.

Silencing of skeletal XXXX -associated genes impairs migration of @entity0 cells and reduces osteolytic bone lesions.

@entity1 :: ('9606', 'Species') :: ['human'] @entity8087 :: ('860', 'Gene') :: ['Runx2'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity1476 :: ('4313', 'Gene') :: ['matrix metalloproteinase 2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour', 'Extraosseous tumour'] @entity75 :: ('MESH:D001927', 'Disease') :: ['reduced skeletal lesions'] @entity3061 :: ('MESH:D010014', 'Disease') :: ['osteolysis'] @entity1096 :: ('6696', 'Gene') :: ['OPN'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity3 :: (MESH:D009362,Disease) :: ['metastasis']
