Impact of stromal and tumor-derived Tenascin-C on breast cancer tumorigenesis and tumor immunity.

We recently developed a new model of breast cancer using orthotopic grafting of mammary tumor cells in immunocompetent syngeneic mice. Tenascin-C (TNC), a matrix molecule expressed during embryogenesis and absent from most adult tissues, is highly produced during tumorigenesis. We investigated the role of stromal TNC, coming from the host, by using wild-type (WT) and knockout (KO) mice for TNC, whereas grafting breast cancer cells with normal (shC) or low (shTNC) expression of TNC (engineered via shRNA knockdown) allowed us to study the impact of TNC expressed by the tumor cells. We then performed a RNA-Seq analysis on tumors prepared 11 weeks after grafting and collected data about genes expression in presence or absence of TNC, coming from the stroma or the cancer cells.

本研究近期构建了一种新型乳腺癌模型，该模型通过在免疫健全同基因小鼠（immunocompetent syngeneic mice）中实施乳腺肿瘤细胞原位移植得以建立。腱生蛋白-C（Tenascin-C，TNC）是一类在胚胎发生阶段表达、于成体多数组织中检测不到的基质分子，在肿瘤发生过程中会大量合成。我们通过构建腱生蛋白-C的野生型（WT）与基因敲除（KO）宿主小鼠，探究了宿主来源的基质源性腱生蛋白-C的功能；同时通过移植经短发夹RNA（shRNA）敲减构建的、正常表达（shC）或低表达（shTNC）腱生蛋白-C的乳腺癌细胞，得以研究肿瘤细胞自身表达的腱生蛋白-C所产生的影响。随后，我们对移植后11周获取的肿瘤组织开展了RNA测序（RNA-Seq）分析，收集了基质或肿瘤细胞来源的腱生蛋白-C存在或缺失状态下的基因表达数据。