Effects of different tissue microenvironments on gene expression in breast cancer cells.

Effects of different tissue microenvironments on gene expression in breast cancer cells.
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DOI:
10.1371/journal.pone.0101160
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Welsh J
Welsh J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rondeau G;Abedinpour P;Desai P;Baron VT;Borgstrom P;Welsh J

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在转移中,循环肿瘤细胞穿透血管壁并进入转移性靶组织,从而暴露于新的和相对不支持的微环境。在新的微环境中,肿瘤细胞通常无限期地保持休眠状态,并且在它们能够成功地定殖组织之前必须适应。人们对这种适应过程知之甚少。我们研究了乳腺癌细胞适应生存和生长的脑,骨髓和肺组织维持在体内培养系统中,作为这些组织的转移性定植模型时,基因表达的时间变化。我们观察到在适应的初始阶段通常与稳态和压力相关的基因的瞬时激活,随后是介导更高级功能的基因的激活,例如细胞形态和细胞分裂的精细化,因为细胞适应于在宿主组织微环境中茁壮成长。我们还观察到宿主组织特征基因的暂时诱导,当肿瘤细胞在脑组织上生长时,这一点特别明显。这些早期瞬时基因表达事件表明了治疗干预的潜在点,而这些点在已确定的肿瘤数据中并不明显。
In metastasis, circulating tumor cells penetrate the walls of blood vessels and enter the metastatic target tissue, thereby becoming exposed to novel and relatively unsupportive microenvironments. In the new microenvironments, the tumor cells often remain in a dormant state indefinitely and must adapt before they are able to successfully colonize the tissue. Very little is known about this adaptive process. We studied temporal changes in gene expression when breast cancer cells adapt to survive and grow on brain, bone marrow, and lung tissue maintained in an in vivo culture system, as models of the metastatic colonization of these tissues. We observed the transient activation of genes typically associated with homeostasis and stress during the initial stages of adaptation, followed by the activation of genes that mediate more advanced functions, such as elaboration of cell morphology and cell division, as the cells adapted to thrive in the host tissue microenvironment. We also observed the temporary induction of genes characteristic of the host tissue, which was particularly evident when tumor cells were grown on brain tissue. These early transient gene expression events suggest potential points of therapeutic intervention that are not evident in data from well-established tumors.
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