Estrogen induces lung metastasis through a host compartment-specific response
Estrogen induces lung metastasis through a host compartment-specific response
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DOI：
10.1158/0008-5472.can-05-4416
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Eliceiri, BP
中科院分区：
文献类型：
--
作者：
Banka, CL;Lund, CV;Eliceiri, BP
雌激素(E(2))对雌激素受体阳性肿瘤的直接增殖作用已有文献报道，但E(2)对影响肿瘤生长和/或转移的选择性宿主效应(即血管生成、血管通透性或间质效应)的潜在作用却鲜有报道。在这项研究中，我们检测了E(2)促进肿瘤生长和/或转移的能力，而不是对肿瘤细胞的直接影响。在这些研究中，我们通过分析植入含有S.C.的卵巢切除(OVX)小鼠的E(2)无反应性肿瘤细胞，区分了E(2)在肿瘤生长和转移中作用的宿主和肿瘤隔室成分。安慰剂(OVX)或含有E(2)的缓释微丸(OVX+E(2))植入物。我们发现D121肺癌细胞系对E(2)无反应，并且遵循S.C.植入OVX与OVX+E(2)相比，E(2)对宿主腔的作用导致自发转移的增加，但不会增加原发肿瘤的生长或新生血管。同样，E(2)无反应的4T1乳腺癌细胞的实验性肺转移也会导致OVX+E(2)小鼠肺部肿瘤负担的增加。这些结果表明，宿主间隔的E(2)状态影响肿瘤细胞转移的晚期步骤，这可以为了解E(2)在肿瘤与宿主间隔中的作用提供重要的见解。
Direct proliferative effects of estrogen (E(2)) on estrogen receptor-positive tumors are well documented; however, the potential for E(2) to mediate effects selective for the host (i.e., angiogenesis, vascular permeability, or stromal effects), which influence tumor growth and/or metastasis, has received less attention. In this study, we examine the capacity for E(2), to promote tumor growth and/or metastasis independent of direct effects on tumor cells. In these studies, we distinguish host versus tumor compartment components of E(2) action in tumor growth and metastasis by analysis of E(2)-nonresponsive tumor cells implanted in ovariectomized (OVX) mice that contain s.c. implants of placebo (OVX) or E(2)-containing slow-release pellets (OVX + E(2)). We show that the D121 lung carcinoma cell line is E(2)-nonresponsive, and following s.c. implantation in OVX versus OVX + E(2), mice, E(2) action on the host compartment leads to an increase in spontaneous metastasis but not primary tumor growth or neovascularization. Similarly, experimental lung metastasis of E(2)-nonresponsive 4T1 mammary carcinoma cells also leads to increased tumor burden in the lungs of OVX + E(2) mice. These results suggest that the E(2) status of the host compartment influences late steps in tumor cell metastasis that can provide important insights into the role of E(2) in the tumor versus host compartments.