Investigating the effects of CSF-1R and PI3Kdelta inhibition on a breast cancer bone metastasis model
Date
2013-01-23
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Abstract
Development of breast cancer-induced bone loss depends on the activation of osteoclasts
by tumor-derived factors that promote osteoclastogenesis and osteolysis. The PI3K
pathway is activated by several of these factors, in particular CSF-1. Given the ability of
PI3K signaling to promote osteoclast survival and activity in a CSF-1R dependent
manner, we hypothesized that inhibition of CSF-1R or PI3K signaling with compounds
GW2580 and ABT-869, and IC87114, respectively, would decrease osteoclast
development and activity leading to decreased osteolysis. Using bioluminescence
imaging and μCT, we identified that GW2580 and ABT-869 significantly decreased
osteolytic lesions and tumor growth in MDA-MB-231 bone metastases. Also, GW2580
increased bone mass in normal C57BL/6 mice, validating the effect of this inhibitor on
CSF-1R-expressing osteoclasts in vivo. Since IC87114 failed to reduce tumor growth and
osteolytic damage, we concluded that CSF-1R signaling, independent of PI3K p110δ
signaling, contributes significantly to tumor growth and to tumor-induced osteolysis in this model.
Description
Keywords
Oncology, Biochemistry
Citation
Salazar-Arcila, C. (2013). Investigating the effects of CSF-1R and PI3Kdelta inhibition on a breast cancer bone metastasis model (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26639