Barbai Tamás, Fejős Zsuzsanna, Puskas Laszlo G, Tímár József, Rásó Erzsébet
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Avidin Ltd., Szeged, Hungary.
Oncotarget. 2015 Oct 6;6(30):29111-28. doi: 10.18632/oncotarget.5059.
We have attempted to characterize the changes occurring on the host side during the progression of human melanoma. To investigate the role of tumor microenvironment, we set up such an animal model, which was able to isolate the host related factors playing central role in metastasis formation. One of these 'factors', CCL12, was consequently selected and its behavior was examined alongside its human homologue (CCL8). In our animal model, metastasis forming primary melanoma in the host exhibited increased level of CCL12 mRNA expression. In clinical samples, when examining the tumor and the host together, the cumulative (tumor and host) CCL8 expression was lower in the group in which human primary melanoma formed lung metastasis compared to non-metastatic primary tumors. We could not detect significant difference in CCL8 receptor (CCR1) expression between the two groups. Increased migration of the examined tumor cell lines was observed when CCL8 was applied as a chemoattractant. The tumor cells and their interactions can be influenced the expression of CCL8 by dermal fibroblasts, as a significant change in the metastatic microenvironment. Furthermore, we examined changes in miRNA profile resulted by CCL8 and miR146a appears to be a promising prognostic marker for following this process.
我们试图描述人类黑色素瘤进展过程中宿主方面发生的变化。为了研究肿瘤微环境的作用，我们建立了这样一种动物模型，它能够分离出在转移形成中起核心作用的宿主相关因素。其中一个“因素”CCL12因此被选中，并与其人类同源物（CCL8）一起研究其行为。在我们的动物模型中，宿主中形成转移的原发性黑色素瘤表现出CCL12 mRNA表达水平升高。在临床样本中，当同时检测肿瘤和宿主时，与非转移性原发性肿瘤相比，人类原发性黑色素瘤形成肺转移的组中累积（肿瘤和宿主）CCL8表达较低。我们在两组之间未检测到CCL8受体（CCR1）表达的显著差异。当将CCL8用作趋化因子时，观察到所检测的肿瘤细胞系迁移增加。肿瘤细胞及其相互作用可受到真皮成纤维细胞对CCL8表达的影响，这是转移微环境中的一个显著变化。此外，我们研究了CCL8导致的miRNA谱变化，miR146a似乎是追踪这一过程的一个有前景的预后标志物。
