Investigating the effects of CSF-1R and PI3Kdelta inhibition on a breast cancer bone metastasis model

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dc.contributor.advisorJirik, Frank
dc.contributor.authorSalazar-Arcila, Carolina
dc.date.accessioned2013-01-23T23:18:46Z
dc.date.available2013-06-15T07:01:47Z
dc.date.issued2013-01-23
dc.date.submitted2013en
dc.description.abstractDevelopment 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.en_US
dc.identifier.citationSalazar-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/26639en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/26639
dc.identifier.urihttp://hdl.handle.net/11023/454
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectOncology
dc.subjectBiochemistry
dc.subject.classificationCSF-1 Receptoren_US
dc.subject.classificationGW2580en_US
dc.subject.classificationBreast cancer bone metastasisen_US
dc.subject.classificationABT-869en_US
dc.subject.classificationMDA-MB-231en_US
dc.titleInvestigating the effects of CSF-1R and PI3Kdelta inhibition on a breast cancer bone metastasis model
dc.typemaster thesis
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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