Overview
Topic status: We're looking for students to study this topic.
Project Summary: Following colonisation of cancer cells in the bone microenvironment significant phenotypic changes occur; breast cancer produces osteolytic lesions characterised by significant bone loss. In contrast prostate cancer produces osteoblastic lesions characterised by significant bone gain. The mechanisms through which these changes in bone mass occur have not been sufficiently explored with most studies being limited to endpoint bone mass data. Preliminary results (Gregory, 2007 unpublished) have indicated that the activity of osteoblasts is significantly regulated by the presence of breast cancer cells. Current literature supports a hypothesis of osteoclast dependent osteolysis in breast cancer metastasis (Zheng et al. 2007). In contrast our results suggest that to minimise metastatic bone lesion development in breast cancer, a treatment which targets osteoblast activity may prove more effective than the current bisphosphonate approach.
Approaches: Following injection of cancer cells into the right tibia of severely combined immuno-deficient mice (Corey et al. 2002), drug treatment will commence either immediately or at a delayed timepoint until sacrifice (sacrifice at 18 or 36 days post-surgery; treatment commences immediately following surgery or at 18 days). This will determine whether cancer-induced bone changes can be prevented, minimised and/or reversed. Limbs will be radiographed post-sacrifice and tibiae extracted for microCT and histological analysis. Using histomorphometric principles, bone architecture (trabecular number, trabecular separation, trabecular width), density (trabecular area, bone tissue area), bone cell activity (mineralising surface, mineral apposition rate, percentage resorption surface), and bone remodelling rates will be calculated and compared between treatment and control limbs/timepoints.
References:
- Corey, E. et al. (2002) Establishment and characterisation of osseous prostate cancer models: intra-tibial injection of human prostate cancer cells. The Prostate 52(1): 20-33.
- Zheng, Y. et al. (2007) Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis.
- Study level
- PhD
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
-
Please contact the supervisor.
Dr Laura Gregory
