Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.
Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.
复制标题
DOI：
10.1371/journal.pone.0014131
复制
发表时间：
2010-11-30
期刊：
影响因子：
3.7
通讯作者：
Amici A
中科院分区：
文献类型：
--
作者：
Marchini C;Montani M;Konstantinidou G;Orrù R;Mannucci S;Ramadori G;Gabrielli F;Baruzzi A;Berton G;Merigo F;Fin S;Iezzi M;Bisaro B;Sbarbati A;Zerani M;Galiè M;Amici A
越来越多的临床和实验证据表明，癌向间充质表型的转变是对治疗的抗性和肿瘤复发的常见范例。然而，间质化的癌尚未进入临床实践作为一个重要的诊断模式。通过将计算机模拟和体外研究与我们的上皮和间充质肿瘤模型相结合，我们在本文中比较了先前描述的癌源性间充质肿瘤细胞（A17）与癌和其他间充质表型（如间充质干细胞（MSC），乳腺基质和各种类型的肉瘤）的关键分子途径。我们确定了A17细胞与MSC和乳腺基质共享的三个间充质/基质标记。通过使用最近开发的计算方法与公开可用的微阵列数据，我们表明这些特征：1）与基底样乳腺癌亚型显著相关; 2）与骨转移显著相关; 3）在激素治疗后上调; 4）预测对新辅助治疗的抵抗。我们的研究结果表明，间充质化是最具侵袭性的肿瘤的内在属性，它与治疗抵抗以及骨转移有关。
Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm. By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies. Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis.