Contribution of Bone Tissue Modulus to Breast Cancer Metastasis to Bone
Contribution of Bone Tissue Modulus to Breast Cancer Metastasis to Bone
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DOI：
10.1007/s12307-011-0078-3
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发表时间：
2011-12-01
影响因子：
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通讯作者：
Sterling, Julie A.
中科院分区：
文献类型：
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作者：
Guelcher, Scott A.;Sterling, Julie A.
某些肿瘤，如乳腺癌，经常转移到骨，在那里它们可以诱导骨破坏。目前，普遍认为肿瘤细胞受到骨微环境中存在的其他细胞和生长因子的影响，导致肿瘤诱导的骨疾病。在过去的20年里，许多研究小组研究了这一过程，并确定了主要的影响因素;然而，这些结果并不能完全解释肿瘤细胞转移到骨时基因表达和细胞行为的变化。最近，研究软组织部位转移的小组已经确定，在软组织中肿瘤进展期间增加的微环境的刚性可以调节肿瘤细胞行为和基因表达。因此，我们开始研究刚性骨细胞外基质在刺激肿瘤诱导的骨病的基因调节中的作用。我们发现，骨的硬度特异性调节甲状旁腺相关蛋白（PTHrP）和Gli 2表达的转化生长因子β（TGF-β）和机械转导依赖的机制。在这篇综述中，我们总结了机械转导信号通路，以及如何影响TGF-β信号和溶骨基因的表达。
Certain tumors, such as breast, frequently metastasize to bone where they can induce bone destruction. Currently, it is well-accepted that the tumor cells are influenced by other cells and growth factors present in the bone microenvironment that lead to tumor-induced bone disease. Over the past 20 years, many groups have studied this process and determined the major contributing factors; however, these results do not fully explain the changes in gene expression and cell behavior that occur when tumor cells metastasize to bone. More recently, groups studying metastasis from soft tissue sites have determined that the rigidity of the microenvironment, which increases during tumor progression in soft tissue, can regulate tumor cell behavior and gene expression. Therefore, we began to investigate the role of the rigid bone extracellular matrix in the regulation of genes that stimulate tumor-induced bone disease. We found that the rigidity of bone specifically regulates parathyroid hormone-related protein (PTHrP) and Gli2 expression in a transforming growth factor beta (TGF-beta) and mechanotransduction-dependent mechanism. In this review, we summarize the mechanotransduction signaling pathway and how this influences TGF-beta signaling and osteolytic gene expression.