Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.
In this study, we fabricated electrospun silica nanofiber membranes and investigated their use in biomolecular sensing. The diameter, porosity and surface-to-volume ratio of nanofiber membranes were investigated under different fabrication conditions. Using this type of nanofiber membrane, enzyme-linked immunosorbent assay (ELISA) was performed, and the results were compared with those obtained with conventional ELISA using polystyrene well plates. The minimum detectable concentration was determined as 0.19 ng ml −1 (1.6 pM), which is 32 times lower than that of conventional ELISA. In addition, the detection time for all processes for the nanofiber membrane was reduced to 1 h, compared with 1 day for conventional ELISA. The increased sensitivity, faster reaction time, and affordability of the nanofiber membrane make it well suited for bio-chip use.
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