Grimm Susanne, Jennek Susanne, Singh Rajan, Enkelmann Astrid, Junker Kerstin, Rippaus Nora, Berndt Alexander, Friedrich Karlheinz
Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
Jena University Hospital, Department of Urology, Jena, Germany.
Exp Cell Res. 2015 Jul 1;335(1):1-11. doi: 10.1016/j.yexcr.2015.04.001. Epub 2015 Apr 22.
The microenvironment of tumor cells is critically involved in tumor development and progression. Tumor-associated fibroblasts (TAFs) represent a major constituent of the tumor stroma. Tumor cells are operative in the activation of TAFs, whereas TAFs in turn contribute to tumor cell malignancy. This report describes mechanisms of communication between fibroblasts and urinary bladder cancer (UBC) cells. Migration of bladder cancer cell lines RT112 and Cal-29, representing two different grades of dedifferentiation, was enhanced by cocultivation with TAFs. Conditioned medium from tumor cells induced the release of interleukin (IL)-8, hepatocyte growth factor (HGF), matrix metalloproteinase-2, granulocyte macrophage colony-stimulating factor, and monocyte chemotactic protein (MCP)-1 by TAFs. Tumor cell-derived IL-1α was identified as a major mediator of these stimulatory effects. Fibroblasts, on the other hand, exerted a migration and invasion stimulating influence on UBC cells. MCP-1 and HGF were shown to promote cell migration of both bladder cancer cell lines.
肿瘤细胞的微环境在肿瘤的发生和发展过程中起着至关重要的作用。肿瘤相关成纤维细胞（TAFs）是肿瘤基质的主要组成部分。肿瘤细胞可激活TAFs，而TAFs反过来又促进肿瘤细胞的恶性化。本报告描述了成纤维细胞与膀胱癌（UBC）细胞之间的通讯机制。与TAFs共培养可增强代表两种不同去分化程度的膀胱癌细胞系RT112和Cal-29的迁移能力。肿瘤细胞的条件培养基可诱导TAFs释放白细胞介素（IL）-8、肝细胞生长因子（HGF）、基质金属蛋白酶-2、粒细胞巨噬细胞集落刺激因子和单核细胞趋化蛋白（MCP）-1。肿瘤细胞衍生的IL-1α被确定为这些刺激作用的主要介质。另一方面，成纤维细胞对UBC细胞具有迁移和侵袭刺激作用。MCP-1和HGF被证明可促进两种膀胱癌细胞系的细胞迁移。
