The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the phenotype of tumoral cells and have significant implications in cancer development and progression. In this study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators. The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the conditioned medium derived from ‘primed’ stromal cells (melanoma-stimulated fibroblasts) was more effective in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from non-stimulated fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment and enable tumoral cells to succeed in the process of melanoma progression and metastasis. Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression and metastasis.

由转化细胞和基质细胞释放的可溶性介体触发的信号传递事件塑造了肿瘤细胞的表型，对癌症的发展和进程具有重要意义。在这项研究中，我们通过评估从恶性黑色素瘤细胞获得的条件培养基刺激后人皮肤成纤维细胞的蛋白质组多样性，进行了体外异型信号分析。此外，我们还评估了用自身条件培养基以及黑色素瘤刺激的成纤维细胞条件培养基刺激后黑色素瘤细胞蛋白质组的变化。我们的研究结果显示，可溶性介体发生串扰后，基质细胞和恶性细胞的蛋白质组发生了明显的重排。黑色素瘤条件培养基刺激的成纤维细胞的主要蛋白质组特征与蛋白质合成有关，这表明该过程可能是基质细胞的早期反应。此外，源自“原始”基质细胞（黑色素瘤刺激的成纤维细胞）的条件培养基在改变恶性细胞的功能表型（细胞迁移）方面比非刺激的成纤维细胞的条件培养基更有效。集体地，自我和交叉刺激可能在塑造肿瘤微环境中起关键作用，并使肿瘤细胞在黑素瘤的进展和转移过程中取得成功。尽管参与这种异型信号传递的细胞的蛋白质组格局代表了高度动态状态的快照，