Browsing by Subject "Bone metastases"

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    Cancer-associated muscle weakness: What’s bone got to do with it?
    (SpringerNature, 2015-05-20) Waning, David L.; Guise, Theresa A.; Department of Medicine, IU School of Medicine
    Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Tumor cells commonly metastasize to bone in advanced cancer to disrupt normal bone remodeling and result in morbidity that includes muscle weakness. Tumor in bone stimulates excessive osteoclast activity, which causes the release of growth factors stored in the mineralized bone matrix. These factors fuel a feed-forward vicious cycle of tumor growth in bone and bone destruction. Recent evidence indicates that these bone-derived growth factors can act systemically to cause muscle weakness. Muscle weakness can be caused by reduced muscle mass or reduced muscle function; in advanced disease, it is likely due to a combination of both reduced quantity and quality of muscle. In this review, we discuss possible mechanisms that lead to skeletal muscle weakness due to bone metastases.
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    Murine models of breast cancer bone metastasis
    (SpringerNature, 2016-05-11) Wright, Laura E.; Ottewell, Penelope D.; Rucci, Nadia; Peyruchaud, Olivier; Pagnotti, Gabriel M.; Chiechi, Antonella; Buijs, Jeroen T.; Sterling, Julie A.; Department of Medicine, School of Medicine
    Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for in vivo and ex vivo assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone.