A Novel Model of Dormancy for Bone Metastatic Breast Cancer Cells
A Novel Model of Dormancy for Bone Metastatic Breast Cancer Cells
复制标题
DOI：
10.1158/0008-5472.can-13-0991
复制
发表时间：
2013-12-01
期刊：
影响因子：
11.2
通讯作者：
Dontu, Gabriela
中科院分区：
文献类型：
--
作者：
Marlow, Rebecca;Honeth, Gabriella;Dontu, Gabriela
乳腺癌患者的死亡率主要是由于疾病的转移性扩散。虽然扩散是乳腺癌的早期事件，但延长的癌细胞休眠期可能导致转移发展的长潜伏期。破译癌细胞休眠和随后在转移部位生长的机制将有助于开发干扰这些过程的策略。这项工作面临的一个挑战是缺乏癌细胞休眠的模型。我们已经建立了新的实验系统来模拟乳腺癌转移生态位的骨微环境。这些系统是基于骨髓中主要细胞类型的乳腺癌细胞的三维共培养。我们确定了癌细胞休眠和增殖的条件。休眠癌细胞能够在转移到支持性微环境中或在控制休眠的信号通路的操纵下增殖。这些实验系统将有助于转移研究，特别是细胞休眠的研究。AACR (C) 2013人。
Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy. (C)2013 AACR.