Breast cancer cell-derived matrix supports vascular morphogenesis
Breast cancer cell-derived matrix supports vascular morphogenesis
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DOI：
10.1152/ajpcell.00011.2012
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发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Gerecht, Sharon
中科院分区：
文献类型：
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作者：
Hielscher, Abigail C.;Qiu, Connie;Gerecht, Sharon
刘伟，刘伟，刘伟.乳腺癌细胞源性基质支持血管形态发生。美国生理学杂志细胞生理学302：C1243-C1256，2012年。首次发表于2012年1月25日; doi：10.1152/ajpcell.00011.2012。细胞外基质（ECM），维持组织稳态的重要，是异常表达的乳腺肿瘤，另外在血管生成中起着至关重要的作用。我们假设乳腺癌细胞（BCC）存款ECM，支持独特的模式血管形态发生的内皮细胞（EC）。ECM表达的评价显示，非致瘤细胞系（MCF 10A）、致瘤细胞系（MCF 7）和转移性细胞系（MDA-MB-231）表达胶原蛋白I和IV、纤连蛋白和层粘连蛋白，其中腱生蛋白-C仅限于MCF 10A和MCF 7。与MCF 7和MDA 231相比，发现由BCC沉积的ECM的量在MCF 10A中更高，所有ECM在其总体结构上不同，但在平均纤维直径上相似。尽管如此，基底细胞癌细胞系的ECM沉积总体上难以检测，并且不足以支持EC的毛细血管样结构（CLS）形成。因此，采用共培养方法，其中将单个BCC系与成纤维细胞共培养。发现沉积的ECM的丰度、ECM蛋白的沉积（例如，来自MDA 231-成纤维细胞共培养物的胶原I沉积的缺失）和原纤维组织的变化。毛细血管特性的评价显示，在从MDA 231-成纤维细胞共培养物沉积的ECM上生长的CLS具有显著更大的管腔直径，占据最大的面积百分比，表达最高水平的血管性血友病因子，并表达最大量的E-选择素，其独立于暴露于TNF-α而上调。据我们所知，这是第一个研究报告肿瘤细胞ECM介导的血管毛细血管特征的差异，从而为未来的调查询问肿瘤ECM在支持血管形态发生中的作用提供了框架。
Hielscher AC, Qiu C, Gerecht S. Breast cancer cell-derived matrix supports vascular morphogenesis. Am J Physiol Cell Physiol 302: C1243-C1256, 2012. First published January 25, 2012; doi:10.1152/ajpcell.00011.2012.-The extracellular matrix (ECM), important for maintaining tissue homeostasis, is abnormally expressed in mammary tumors and additionally plays a crucial role in angiogenesis. We hypothesize that breast cancer cells (BCCs) deposit ECM that supports unique patterns of vascular morphogenesis of endothelial cells (ECs). Evaluation of ECM expression revealed that a nontumorigenic cell line (MCF10A), a tumorigenic cell line (MCF7), and a metastatic cell line (MDA-MB-231) express collagens I and IV, fibronectin, and laminin, with tenascin-C limited to MCF10A and MCF7. The amount of ECM deposited by BCCs was found to be higher in MCF10A compared with MCF7 and MDA231, with all ECM differing in their gross structure but similar in mean fiber diameter. Nonetheless, deposition of ECM from BCC lines was overall difficult to detect and insufficient to support capillary-like structure (CLS) formation of ECs. Therefore, a coculture approach was undertaken in which individual BCC lines were cocultured with fibroblasts. Variation in abundance of deposited ECM, deposition of ECM proteins, such as absent collagen I deposition from MDA231-fibroblast cocultures, and fibril organization was found. Deposited ECM from fibroblasts and each coculture supported rapid CLS formation of ECs. Evaluation of capillary properties revealed that CLS grown on ECM deposited from MDA231-fibroblast cocultures possessed significantly larger lumen diameters, occupied the greatest percentage of area, expressed the highest levels of von Willebrand factor, and expressed the greatest amount of E-selectin, which was upregulated independent of exposure to TNF-alpha. To our knowledge, this is the first study to report tumor cell ECM-mediated differences in vascular capillary features, and thus offers the framework for future investigations interrogating the role of the tumor ECM in supporting vascular morphogenesis.