Genetic Immunization Laboratory, Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy.
PLoS One. 2010 Nov 30;5(11):e14131. doi: 10.1371/journal.pone.0014131.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
越来越多的临床和实验证据表明，癌细胞向间充质表型的转变是治疗抵抗和肿瘤复发的共同模式。然而，癌细胞的间充质化尚未作为一个关键的诊断模式进入临床实践。
方法/主要发现：通过整合计算机和体外研究以及我们的上皮和间充质肿瘤模型，我们在此比较了先前描述的癌源性间充质肿瘤细胞（A17）与癌以及其他间充质表型（如间充质干细胞[MSCs]、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 MSCs 和乳腺基质共有的三个间充质/基质特征。通过使用最近开发的基于公共微阵列数据的计算方法，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耐药性。
结论/意义：我们的结果表明，间充质化是最具侵袭性肿瘤的内在特性，它与治疗抵抗以及骨转移有关。
