HIF targets in bone remodeling and metastatic disease.
HIF targets in bone remodeling and metastatic disease.
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DOI：
10.1016/j.pharmthera.2015.02.002
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发表时间：
2015-06
影响因子：
13.5
通讯作者：
Giaccia, Amato J.
中科院分区：
文献类型：
--
作者：
Johnson, Rachelle W.;Schipani, Ernestina;Giaccia, Amato J.
骨髓伊萨一种缺氧的微环境，富含生长因子和血管，并且容易被从许多癌症（包括乳腺癌、前列腺癌、肺癌和皮肤肿瘤）传播的肿瘤细胞定殖。扩散到骨髓的肿瘤细胞的转移性生长促进因子来源于多种来源：骨基质，其是生长因子的储存库，以及驻留在骨髓中和沿着骨表面的细胞，如成骨细胞、破骨细胞、巨噬细胞和T细胞，其分泌细胞因子和趋化因子。骨髓内的低氧水平诱导低氧信号传导途径，例如低氧诱导因子（HIF），其由需氧脯氨酰羟化酶（PHD）和von Hippel-Lindau（VHL）肿瘤抑制因子调节。这些缺氧信号通路对骨发育和体内平衡具有深远的影响。同样，在局部乳腺和前列腺肿瘤中观察到的低氧条件表明低氧诱导基因在骨髓转移和定植中的作用。这篇综述将探讨低氧调节因子在骨发育和重建中的作用，以及这些因子如何促进实体瘤骨转移。
The bone marrow isa hypoxic microenvironment that is rich in growth factors and blood vessels and is readily colonized by tumor cells disseminated from numerous cancers including tumors of the breast, prostate, lung, and skin. The origin of metastatic growth promoting factors for tumor cells disseminated to the bone marrow is derived from multiple sources: the bone matrix, which is a reservoir for growth factors, and cells residing in the marrow and along bone surfaces, such as osteoblasts, osteoclasts, macrophages, and T cells, which secrete cytokines and chemokines. Low oxygen levels within the bone marrow induce hypoxia signaling pathways such as hypoxia inducible factor (HIF), which is regulated by oxygen requiring prolyl hydroxylases (PHDs) and von Hippel–Lindau (VHL) tumor suppressor. These hypoxia signaling pathways have profound effects on bone development and homeostasis. Likewise, hypoxic conditions observed in local breast and prostate tumors point to a role for hypoxia-inducible genes in metastasis to and colonization of the bone marrow. This review will explore the role of hypoxia-regulated factors in bone development and remodeling, and how these elements may contribute to solid tumor metastasis to the bone.
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影响因子：
23.4
作者：
Gartrell BA;Coleman RE;Fizazi K;Miller K;Saad F;Sternberg CN;Galsky MD
通讯作者：
Galsky MD
影响因子：
3.4
作者：
Chow, DC;Wenning, LA;Papoutsakis, ET
通讯作者：
Papoutsakis, ET
影响因子：
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Amarilio, Roy;Viukov, Sergey V.;Zelzer, Elazar
通讯作者：
Zelzer, Elazar
影响因子：
11.2
作者：
Catena, Raul;Luis-Ravelo, Diego;Lecanda, Fernando
通讯作者：
Lecanda, Fernando
影响因子：
11.5
作者：
Coleman, Robert E.
通讯作者：
Coleman, Robert E.