Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Pathology. 2013 Aug;45(5):443-52. doi: 10.1097/PAT.0b013e328363b3bd.
Melanoma cells interact with and depend on seemingly normal cells in their tumour microenvironment to allow the acquisition of the hallmarks of solid cancer. In general, there are three types of interaction of melanoma cells with their microenvironment. First, there is bilateral communication between melanoma cells and the stroma, which includes fibroblasts, endothelial cells, immune cells, soluble molecules, and the extracellular matrix. Second, while under normal conditions keratinocytes control localisation and proliferative behaviour of melanocytes in the epidermis, once this balance is disturbed and a melanoma has developed, melanoma cells may take over the control of their epidermal tumour microenvironment. Finally, there are subcompartments within tumours with different microenvironmental milieu defined by their access to oxygen and nutrients. Therefore, different melanoma cells within a tumour face different microenvironments. Interactions between melanoma cells among each other and with the cell types in their microenvironment happen through endocrine and paracrine communication and/or through direct contact via cell-cell and cell-matrix adhesion, and gap junctional intercellular communication (GJIC). Connexins have been identified as key molecules for direct cell-cell communication and are also thought to be important for the release of signalling molecules from cells to the microenvironment. In this review we provide an update of the alterations in cell-cell communication in melanoma and the tumour microenvironment associated with melanoma development and progression.
黑色素瘤细胞与其肿瘤微环境中的看似正常细胞相互作用并依赖这些细胞，从而获得实体瘤的标志性特征。一般来说，黑色素瘤细胞与其微环境之间存在三种相互作用类型。首先，黑色素瘤细胞与基质之间存在双向通讯，其中包括成纤维细胞、内皮细胞、免疫细胞、可溶性分子和细胞外基质。其次，在正常情况下，角质形成细胞控制表皮中黑素细胞的定位和增殖行为，但一旦这种平衡被打破且黑色素瘤发生，黑色素瘤细胞可能会接管其表皮肿瘤微环境的控制。最后，肿瘤内存在不同的亚区，其微环境因氧气和营养物质的获取而不同。因此，肿瘤内的不同黑色素瘤细胞面临着不同的微环境。黑色素瘤细胞之间以及与微环境中细胞类型之间的相互作用是通过内分泌和旁分泌通讯以及通过细胞-细胞和细胞-基质黏附以及缝隙连接细胞间通讯（GJIC）的直接接触来发生的。连接蛋白已被确定为直接细胞-细胞通讯的关键分子，并且它们对于细胞向微环境释放信号分子也很重要。在这篇综述中，我们提供了黑色素瘤细胞间通讯以及与黑色素瘤发生和进展相关的肿瘤微环境中细胞通讯改变的最新信息。
