Murine models of breast cancer bone metastasis

Murine models of breast cancer bone metastasis
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DOI:
10.1038/bonekey.2016.31
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发表时间:
2016-05-11
期刊:
BONEKEY REPORTS
影响因子:
--
通讯作者:
Sterling, Julie A.
Sterling, Julie A.
中科院分区:
其他
文献类型:
--
作者:
Wright, Laura E.;Ottewell, Penelope D.;Sterling, Julie A.

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骨转移在晚期乳腺癌患者中会导致显著的发病率和死亡率,目前被认为是无法治愈的。研究人员依靠翻译模型来更好地了解恶性肿瘤骨骼并发症的发病机制,以便确定最终可能预防和治疗实体肿瘤骨转移的治疗靶点。今天,许多乳腺癌骨转移的实验模型都在使用,每个模型都有自己的警告。在这篇方法综述中,我们描述了常用的人和鼠来源的乳腺细胞系的骨表型,这些细胞系在小鼠中引起成骨和/或骨溶解破坏,并报告了在小鼠骨转移模型中优化肿瘤摄取的方法。然后,我们提供了四种最常见的异种和同基因接种方法,用于模拟乳腺癌向小鼠骨骼的转移,包括心脏内、动脉内、原位和胫骨内注射肿瘤细胞的方法。提供了对肿瘤进展和骨破坏的体内和体外评估的建议,随后讨论了可用工具和转换模型的优点和局限性,这些工具和转换模型帮助研究人员研究乳腺癌向骨的转移。
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. Wethen 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.