Studying the Effects of Bone Morphogenetic Protein-2 on Osteosarcoma Tumour Biology

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dc.contributor.advisorMonument, Michael
dc.contributor.advisorJirik, Frank
dc.contributor.authorKendal, Joseph
dc.contributor.committeememberMahoney, Douglas
dc.contributor.committeememberSchneider, Prism
dc.date.accessioned2019-01-07T17:20:50Z
dc.date.available2019-01-07T17:20:50Z
dc.date.issued2019-01-04
dc.description.abstractImpaired bone healing biology in osteosarcoma patients contributes to significant local complications following limb salvage surgery. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has potential to mitigate these complications; however, its use is limited due to concerns of pro-oncogenic signalling. Conversely, recent pre-clinical studies suggest BMP-2 may induce osteosarcoma differentiation. We assessed the oncologic consequences of BMP-2 signalling on osteosarcoma in vitro and in vivo. Two human (143b and SaOS-2) and one syngeneic mouse (DLM8-M1) osteosarcoma cell lines were engineered to up-regulate BMP-2. Xenograft orthotopic murine models were used to assess the effects of exogenous and endogenous elevations in BMP-2 signaling on tumour growth and metastasis. Tumour burden was quantified using tumour volume measurements, bioluminescence and micro-CT. In the 143b cell line there was no differentiation response, however cellular proliferation, motility and tumour growth were enhanced with BMP-2. The SaOS-2 cell line was found to be more differentiated than the 143b cell line and responded to BMP-2 signalling with partial osteoblastic differentiation, and a reduction in in vivo local tumour burden. Rates of lung metastasis were unchanged in both 143b and SaOS-2. BMP-2 upregulation in the DLM8-M1 cell line induced a partial differentiation response; in vivo studies are ongoing. The observed divergent effects of BMP-2 on osteosarcoma tumour growth may be due to the variation in intrinsic differentiation abilities of different cell lines. Importantly, these results do not support the clinical application of BMP-2 in osteosarcoma limb salvage surgery due to the potential for stimulating growth of any microscopic tumour burden.en_US
dc.identifier.citationKendal, J.K. (2019). Studying the Effects of Bone Morphogenetic Protein-2 on Osteosarcoma Tumour Biology (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/35704
dc.identifier.urihttp://hdl.handle.net/1880/109433
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
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.en_US
dc.subjectOsteosarcomaen_US
dc.subjectBMP-2en_US
dc.subjectLimb salvageen_US
dc.subjectOsteogenic differentiationen_US
dc.subjectMetastasisen_US
dc.subjectOrthotopic tumour modelen_US
dc.subjectOrthopaedic surgeryen_US
dc.subjectRecombinant human bone morphogenetic protein-2en_US
dc.subject.classificationMedicine and Surgeryen_US
dc.subject.classificationOncologyen_US
dc.titleStudying the Effects of Bone Morphogenetic Protein-2 on Osteosarcoma Tumour Biologyen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Medical Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrue
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