Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Pordenone, Italy.
Cell Cycle. 2012 Nov 15;11(22):4242-51. doi: 10.4161/cc.22543. Epub 2012 Oct 24.
Increasing evidence indicates that invasive properties of breast cancers rely on gain of mesenchymal and stem features, which has suggested that the dual targeting of these phenotypes may represent an appealing therapeutic strategy. It is known that the fraction of stem cells can be enriched by culturing breast cancer cells as mammospheres (MS), but whether these pro-stem conditions favor also the expansion of cells provided of mesenchymal features is still undefined. In the attempt to shed light on this issue, we compared the phenotypes of a panel of 10 breast cancer cell lines representative of distinct subtypes (luminal, HER2-positive, basal-like and claudin-low), grown in adherent conditions and as mammospheres. Under MS-proficient conditions, the increment in the fraction of stem-like cells was associated to upregulation of the mesenchymal marker Vimentin and downregulation of the epithelial markers expressed by luminal cells (E-cadherin, KRT18, KRT19, ESR1). Luminal cells tended also to upregulate the myoepithelial marker CD10. Taken together, our data indicate that MS-proficient conditions do favor mesenchymal/myoepithelial features, and indicate that the use of mammospheres as an in vitro tumor model may efficiently allow the exploitation of therapeutic approaches aimed at targeting aggressive tumors that have undergone epithelial-to-mesenchymal transition
越来越多的证据表明，乳腺癌的侵袭性特征依赖于间质和干细胞特征的获得，这表明针对这些表型的双重靶向可能代表一种有吸引力的治疗策略。已知可以通过将乳腺癌细胞培养为乳腺球体（MS）来富集干细胞分数，但这些促进干细胞的条件是否也有利于具有间质特征的细胞的扩增尚不清楚。为了阐明这个问题，我们比较了 10 个代表不同亚型（腔型、HER2 阳性、基底样和 Claudin-低）的乳腺癌细胞系的表型，这些细胞系在贴壁条件下和乳腺球体中生长。在 MS 有能力的条件下，干细胞样细胞分数的增加与间质标志物波形蛋白的上调和腔型细胞表达的上皮标志物（E-钙黏蛋白、KRT18、KRT19、ESR1）的下调有关。腔型细胞也倾向于上调肌上皮标志物 CD10。总之，我们的数据表明，MS 有能力的条件确实有利于间质/肌上皮特征，并表明使用乳腺球体作为体外肿瘤模型可以有效地利用旨在靶向经历上皮-间充质转化的侵袭性肿瘤的治疗方法。
