摘要
骨骼是癌症类型中转移性生长最常见和最危险的部位之一,骨转移仍然无法治愈。不幸的是,癌症优先转移到骨骼的过程还不太清楚。在本综述中,我们总结了使骨骼成为转移和骨重建的独特位点的形态特征,物理特性和细胞信号传导事件。肿瘤细胞和骨细胞之间的信号串扰开始恶性循环 - 肿瘤细胞与由破骨细胞,成骨细胞,其他骨髓细胞,骨基质和脉管系统组成的骨微环境之间的自我维持的反馈环路,以支持肿瘤生长和骨破坏。通过这种串扰,骨骼提供了一种肥沃的微环境,可以长期存在休眠的肿瘤细胞,并且通过释放细胞因子来支持其生长,因为骨基质被破坏,类似于为种子在土壤中发芽提供营养。然而,很少有模型研究转移性肿瘤细胞的骨定植后期。我们描述了用于研究骨转移的一些现有方法,突出了这些方法的局限性和用于研究骨转移的替代未来策略。虽然体内动物和患者研究可能提供用于研究转移的黄金标准,但是离体模型可以用作替代方案,以实现旨在研究骨转移晚期阶段的更受控制的实验。
关键词: 骨转移模型,肿瘤微环境,生物反应器,骨髓,癌症。
Current Drug Targets
Title:Bone: A Fertile Soil for Cancer Metastasis
Volume: 18 Issue: 11
关键词: 骨转移模型,肿瘤微环境,生物反应器,骨髓,癌症。
摘要: Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. Unfortunately, the processes by which cancers preferentially metastasize to bone are still not well understood. In this review, we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle – a self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction. Through this crosstalk, bone provides a fertile microenvironment that can harbor dormant tumor cells, sometimes for long periods, and support their growth by releasing cytokines as the bone matrix is destroyed, similar to providing nutrients for a seed to germinate in soil. However, few models exist to study the late stages of bone colonization by metastatic tumor cells. We describe some of the current methodologies used to study bone metastasis, highlighting the limitations of these methods and alternative future strategies to be used to study bone metastasis. While in vivo animal and patient studies may provide the gold standard for studying metastasis, ex vivo models can be used as an alternative to enable more controlled experiments designed to study the late stages of bone metastasis.
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Cite this article as:
Bone: A Fertile Soil for Cancer Metastasis, Current Drug Targets 2017; 18 (11) . https://dx.doi.org/10.2174/1389450117666161226121650
DOI https://dx.doi.org/10.2174/1389450117666161226121650 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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