Targeting tumor-stromal interactions in bone metastasis.
Targeting tumor-stromal interactions in bone metastasis.
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DOI：
10.1016/j.pharmthera.2013.10.006
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发表时间：
2014-02
影响因子：
13.5
通讯作者：
Kang, Yibin
中科院分区：
文献类型：
--
作者：
Esposito, Mark;Kang, Yibin
关键词：
骨转移是晚期实体瘤中常见的情况，包括乳腺癌、前列腺癌或肺癌。然而，这种倾向的原因直到最近才被阐明。在过去的十年中，在理解骨转移的分子基础方面取得了重大进展，并且这些研究的大部分揭示了宿主基质在转移级联的每个步骤中的关键作用。肿瘤-基质相互作用在构建转移前小生境、适应转移性种植和建立骨转移恶性循环中至关重要。目前骨转移的治疗集中在转移级联的后期步骤，大多数治疗针对骨重建的过程;然而，新兴的研究确定了许多其他候选人作为有希望的目标。包括血小板和内皮细胞在内的宿主基质细胞在转移归巢、附着和外渗的早期步骤中是重要的，而骨髓的各种免疫细胞、实质细胞和间充质细胞在建立明显的免疫抑制转移性病变中是重要的。这些步骤中的许多参与者已经被确定并进行了功能验证。重要贡献者包括整合素（αvβ3、α2β1、α4β1）、TGFβ家族成员、骨驻留蛋白（BSP、OPG、OPN、RANKL和PTHrP）。在这篇综述中，我们将讨论宿主基质细胞的贡献转移前的小生境调节，播种，休眠，骨重建，免疫调节，和化疗屏蔽骨转移。探索骨转移和基质细胞之间的这些相互作用的研究已经产生了许多治疗靶点，我们将讨论当前和未来治疗骨转移的治疗途径。
Bone metastasis is a frequent occurrence in late stage solid tumors, including breast cancers, prostate or lung. However, the causes for this proclivity have only recently been elucidated. Significant progress has been made in the past decade toward understanding the molecular underpinnings of bone metastasis, and much of this research reveals a crucial role of the host stroma in each step of the metastatic cascade. Tumor-stromal interactions are crucial in engineering a pre-metastatic niche, accommodating metastatic seeding, and establishing the vicious cycle of bone metastasis. Current treatments in bone metastasis focus on latter steps of the metastatic cascade, with most treatments targeting the process of bone remodeling; however, emerging research identifies many other candidates as promising targets. Host stromal cells including platelets and endothelial cells are important in the early steps of metastatic homing, attachment and extravasation while a variety of immune cells, parenchymal cells and mesenchymal cells of the bone marrow are important in the establishment of overt, immune-suppressed metastatic lesions. Many participants during these steps have been identified and functionally validated. Significant contributors include integrins, (αvβ3, α2β1, α4β1), TGFβ family members, bone resident proteins (BSP, OPG, SPARC, OPN), RANKL, and PTHrP. In this review, we will discuss the contribution of host stromal cells to pre-metastatic niche conditioning, seeding, dormancy, bone-remodeling, immune regulation, and chemotherapeutic shielding in bone metastasis. Research exploring these interactions between bone metastases and stromal cells has yielded many therapeutic targets, and we will discuss both the current and future therapeutic avenues in treating bone metastasis.
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影响因子：
64.5
作者：
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影响因子：
20.3
作者：
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通讯作者：
Matsumoto, T