Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer Res. 2011 Nov 1;71(21):6561-6. doi: 10.1158/0008-5472.CAN-11-1432. Epub 2011 Oct 18.
Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients.
黑色素瘤的进展取决于肿瘤细胞与相邻微环境之间的串扰。凝血酶受体，蛋白酶激活受体-1（PAR-1），在黑色素瘤进展过程中发挥着关键作用。PAR-1 及其激活因子在肿瘤细胞及其周围基质上表达，不仅诱导凝血，还诱导细胞信号转导，促进转移表型。最近已经确定了几种粘附分子、细胞因子、生长因子和蛋白酶作为 PAR-1 的下游靶点，并已证明它们可以调节黑色素瘤生长和转移过程中肿瘤细胞与微环境之间的相互作用。通过靶向 PAR-1 抑制这些相互作用可能是黑色素瘤患者的一种有用的治疗方式。
