The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis
The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis
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DOI：
10.1158/2159-8290.cd-16-0822
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发表时间：
2017-02-01
期刊：
影响因子：
28.2
通讯作者：
Schedin, Pepper
中科院分区：
文献类型：
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作者：
Goddard, Erica T.;Hill, Ryan C.;Schedin, Pepper
与年龄匹配的未经产或妊娠患者相比，产后乳腺癌患者的转移风险增加。在这里，我们解决了循环肿瘤细胞是否在产后宿主中具有转移优势，并发现泌乳后啮齿动物肝脏优先支持转移。在断奶后，我们观察到肝脏重量减轻，肝细胞凋亡，细胞外基质重塑，包括胶原蛋白和生腱蛋白-C的沉积，以及骨髓细胞浸润，这些数据与断奶诱导的肝脏退化和建立促转移微环境一致。使用心内和门静脉内转移模型，我们观察到断奶后的BALB/c小鼠与未经生产的对照组相比，肝转移增加。产后乳腺癌患者（n = 564）的肝转移增加了3倍，肝特异性嗜性（n = 117）提示了人类相关性。总之，我们的数据揭示了一个以前未知的啮齿类动物肝脏的生物学，断奶引起的肝脏退化，这可能会提供洞察到增加的肝转移和产后乳腺癌诊断的妇女预后不良。意义：我们发现，产后乳腺癌患者肝转移的风险增加。我们发现了一种以前未被认识到的生物学，即断奶诱导的肝脏退化，建立了一个促转移的微环境，这可能是产后乳腺癌患者预后不良的部分原因。(C)2017年AACR。
Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and fi nd the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell infl ux, data consistent with weaning-induced liver involution and establishment of a prometastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning BALB/c mice compared with nulliparous controls. Human relevance is suggested by a similar to 3-fold increase in liver metastasis in patients with postpartum breast cancer (n = 564) and by liver-specifi c tropism (n = 117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer.SIGNIFICANCE: We fi nd that patients with postpartum breast cancer are at elevated risk for liver metastasis. We identify a previously unrecognized biology, namely weaning-induced liver involution, that establishes a prometastatic microenvironment, and which may account in part for the poor prognosis of patients with postpartum breast cancer. (C) 2017 AACR.