Spatial organization of the tenascin-C microenvironment in experimental and human cancer

The extracellular matrix (ECM) molecule tenascin-C (TNC) promotes tumor progression. This has recently been demonstrated in the stochastic murine RIP1-Tag2 insulinoma model, engineered to either express TNC abundantly or to be devoid of TNC. However, our knowledge about organization of the TNC microenvironment is scant. Here we determined the spatial distribution of TNC together with other ECM molecules in murine RIP1-Tag2 insulinoma and human cancer tissue (insulinoma and colorectal carcinoma). We found that TNC is organized in matrix tracks together with other ECM molecules of the AngioMatrix signature, a previously described gene expression profile that characterizes the angiogenic switch. Moreover, stromal cells including endothelial cells, fibroblasts and leukocytes were enriched in the TNC tracks. Thus, TNC tracks may provide niches for stromal cells and regulate their behavior. Given similarities of TNC rich niches for stromal cells in human insulinoma and colon cancer, we propose that the RIP1-Tag2 model may be useful for providing insights into the contribution of the tumor stroma specific ECM as promoter of cancer progression.

细胞外基质（extracellular matrix, ECM）分子腱生蛋白-C（tenascin-C, TNC）可促进肿瘤进展。近期这一结论在随机小鼠RIP1-Tag2胰岛素瘤模型中得到验证——该模型经基因工程改造后，可实现TNC的高表达或完全缺失。然而，目前学界对TNC微环境的组织模式仍知之甚少。本研究检测了小鼠RIP1-Tag2胰岛素瘤以及人类癌组织（包括胰岛素瘤与结直肠癌）中TNC与其他细胞外基质分子的空间分布特征。研究发现，TNC与血管生成特征基因谱（AngioMatrix signature）所涵盖的其他细胞外基质分子共同构成基质轨道；该基因谱是此前已报道的、用于表征血管生成转换的基因表达特征。此外，内皮细胞、成纤维细胞与白细胞等基质细胞在TNC基质轨道中显著富集。据此可知，TNC基质轨道可为基质细胞提供龛位，并调控其生物学行为。鉴于人类胰岛素瘤与结肠癌中富含TNC的基质细胞龛具有相似性，我们认为RIP1-Tag2模型可用于揭示肿瘤基质特异性细胞外基质作为肿瘤进展促进因子的具体作用。