Luminal breast cancer metastasis is dependent on estrogen signaling.
Luminal breast cancer metastasis is dependent on estrogen signaling.
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DOI：
10.1007/s10585-012-9466-4
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发表时间：
2012-06
影响因子：
4
通讯作者：
Reiss, Michael
中科院分区：
文献类型：
--
作者：
Ganapathy, Vidya;Banach-Petrosky, Whitney;Xie, Wen;Kareddula, Aparna;Nienhuis, Hilde;Miles, Gregory;Reiss, Michael
管腔性乳腺癌是最常见的人类乳腺癌类型，占所有因转移性疾病导致的乳腺癌死亡的一半。我们已经开发出了新的体内模型的播散性人腔乳腺癌，密切模仿人类疾病。从胫骨的初始病变开始，可预见局部转移沿着髂和腹膜后淋巴结链发展。肿瘤细胞在整个扩散过程中保持其上皮样表型。此外，全身注射的转移性MCF-7细胞始终引起骨骼、口底、肾上腺以及肺、肝、脑和乳腺脂肪垫中的转移。我们发现，腔乳腺癌转移的增长是高度依赖于雌激素的剂量依赖性的方式和雌激素撤退诱导转移性疾病的快速生长停滞。另一方面，即使在没有雌激素的情况下，继发部位的微转移灶仍然存在，但它们处于休眠状态，不会进展为大转移灶。因此，归巢和播种二级网站不需要雌激素。此外，与其中转化生长因子-β信号传导起关键作用的基底样乳腺癌转移形成鲜明对比，管腔乳腺癌转移不依赖于该细胞因子。这些发现对管腔型乳腺癌靶向抗转移治疗的发展具有重要意义。
Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains. Tumors cells retain their epithelioid phenotype throughout the process of dissemination. In addition, systemically injected metastatic MCF-7 cells consistently give rise to metastases in the skeleton, floor of mouth, adrenal glands, as well as in the lungs, liver, brain and mammary fat pad. We show that growth of luminal breast cancer metastases is highly dependent on estrogen in a dose-dependent manner and that estrogen withdrawal induces rapid growth arrest of metastatic disease. On the other hand, even though micrometastases at secondary sites remain viable in the absence of estrogen, they are dormant and do not progress to macrometastases. Thus, homing to and seeding of secondary sites do not require estrogen. Moreover, in sharp contrast to basal-like breast cancer metastasis in which transforming growth factor-β signaling plays a key role, luminal breast cancer metastasis is independent of this cytokine. These findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer.
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影响因子：
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作者：
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