Gene expression profiling reveals cross-talk between melanoma and fibroblasts: Implications for host-tumor interactions in metastasis
Gene expression profiling reveals cross-talk between melanoma and fibroblasts: Implications for host-tumor interactions in metastasis
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DOI：
10.1158/0008-5472.can-04-0415
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发表时间：
2005-05-15
期刊：
影响因子：
11.2
通讯作者：
Fox, JW
中科院分区：
文献类型：
--
作者：
Gallagher, PG;Bao, YD;Fox, JW
宿主-肿瘤相互作用被认为在癌发生、肿瘤侵袭和转移中至关重要。为了探索宿主-肿瘤相互作用的相互作用，我们开发了一个系统来评估在纤维胶原与HS-68原代人成纤维细胞中共培养的A2058人黑色素瘤细胞的基因表达模式。共培养的A2058细胞的基因表达模式仅受到轻微影响，而HS-68成纤维细胞的基因表达模式发生了显着改变。白细胞介素-11和抑制剂的DNA结合域-1基因的表达在共培养的A2058细胞下调，分别表示促炎反应和抗凋亡。上调基因的总体模式表明促炎过程的触发。此外，黑色素瘤生长和迁移刺激趋化因子CXCL 1和CXCL 2在共培养的成纤维细胞中显著上调。这些结果得到了证实的额外的共培养实验与黑色素瘤细胞系WM-164，BLM，SK-Mel-28和免疫组化的侵袭性人黑色素瘤切片。总之，这些结果表明，肿瘤细胞在基质成纤维细胞中引起促炎和黑色素瘤生长促进反应。炎症在致癌、肿瘤促进、侵袭和转移中的作用被认为越来越重要，这些研究的结果强调了这一点，并确定了某些关键蛋白质，这些蛋白质是宿主-肿瘤微环境中复杂的相互作用过程的结果。
Host-tumor interaction is considered critical in carcinogenesis, tumor invasion, and metastasis. To explore the reciprocal effects of host-tumor interaction, we developed a system to assess the gene expression patterns of A2058 human melanoma cells cocultured in fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered. Interleukin-11 and inhibitor of DNA-binding domain-1 gene expression in the cocultured A2058 cells was down-regulated, indicative of a proinflammatory response and resistance to apoptosis, respectively. The overall pattern of up-regulated genes indicated triggering of the proinflammatory process. In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts. These results were corroborated by additional coculture experiments with the melanoma cell lines WM-164, BLM, and SK-Mel-28 and immunohistochemistry on invasive human melanoma sections. Taken together, these results indicate that tumor cells cause a proinflammatory and melanoma growth-promoting response in stromal fibroblasts. The role of inflammation in carcinogenesis, tumor promotion, invasion, and metastasis is viewed as being increasingly important and the results of these studies underscore this as well as identify certain key proteins that are expressed as a result of the complex interactive processes in the host-tumor microenvironment.