Snai2 influences breast cancer evolution in a non-cell autonomous manner

SNAI2 is a transcription factor involved in multiple processes in both physiology and pathology, including apoptosis, epithelial-mesenchymal transition and tumorigenesis. The effects of SNAI2 on the epithelial compartment have been interpreted as an effect of its expression and action in that compartment. In this work, we demonstrated that the absence of Snai2 in other compartments has repercussions in different aspects of the behavior of the epithelial cells of luminal breast tumors, developed by MMTV-ErbB2/Neu transgenic mice that do not express SNAI2 in the epithelial component. The absent of SNAI2 in the stroma of these tumors is accompanied by different characteristics at histopathological and molecular levels than those having functional SNAI2. These results indicate that the expression of SNAI2 in the tumor niche contributes to the luminal tumor development and behavior. Mice were housed at the Animal Research Core Facility of the University of Salamanca. FVB/N-Tg(MMTVneu)202Mul/J, carrying the ErbB2 protooncogene (Guy et al., 1992) were obtained from the Jackson Laboratory. B6;129S1-Snai2tm2Grid/J Snai2-deficient mice were generated by Dr. Gridley (Jiang et al., 1998) To generate the parous cohort, Snai2 WT ERBB2+ and Snai2 KO

SNAI2是一种参与生理与病理过程多个环节的转录因子（transcription factor），涵盖细胞凋亡（apoptosis）、上皮间质转化（epithelial-mesenchymal transition）以及肿瘤发生（tumorigenesis）。此前学界认为，SNAI2对上皮细胞组分的调控作用源于其在上皮组分内的表达与功能。本研究证实，在不于上皮组分中表达SNAI2的MMTV-ErbB2/Neu转基因小鼠所诱导的管腔型乳腺肿瘤中，其他微环境组分缺失Snai2会对上皮细胞的多种行为特征产生影响。与保留功能性SNAI2的肿瘤相比，这类肿瘤的间质缺失SNAI2时，其组织病理学与分子层面均呈现出独特的特征。上述结果表明，SNAI2在肿瘤微环境龛（tumor niche）中的表达可促进管腔型乳腺肿瘤的发生发展与行为特征。实验小鼠饲养于萨拉曼卡大学动物研究核心设施中。携带ErbB2原癌基因（protooncogene）的FVB/N-Tg(MMTVneu)202Mul/J小鼠购自杰克逊实验室（Jackson Laboratory，相关研究参见Guy等人1992年的工作）。B6;129S1-Snai2tm2Grid/J Snai2基因敲除小鼠由Gridley博士构建（相关研究参见Jiang等人1998年的工作）。为构建经产小鼠队列，本研究使用了Snai2野生型ERBB2阳性与Snai2基因敲除小鼠。