Cancer cells rewire metabolism to sustain high proliferation rates. Beside glycolysis and glutaminolysis, amino acids substitute as energy source, feed fatty acid biosynthesis and represent part of the secretome of transformed cells, including melanoma. We have therefore investigated acetate, pyruvate and the amino acid composition of the secretome of human melanoma cells representing the early slow (WM35, WM278, WM793b and VM21) and metastatic fast (A375, 518a2, 6F and WM8) growth phase in order to identify possible signalling components within these profiles. Proliferation assays and a principle component analysis revealed a stringent difference between the fast and slow growing melanoma cells. Moreover, upon inhibition of the mevalonate pathway, glutamic acid and alanine were identified as the central difference in the conditional media. A supplementation of the media with glutamic acid and the combination with alanine significantly accelerated the proliferation, migration and invasion of early stage melanoma cells, but not metastatic cells. Finally, the inhibition of the mevalonate pathway abolished the growth advantage of the melanoma cells in a time dependent manner. Taken together, these data corroborate a stage specific response in growth and aggressiveness to extracellular glutamic acid and alanine, indicative for microenvironmental signalling of individual amino acids.

中文翻译：

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不同疾病阶段的人黑素瘤细胞系中的氨基酸特征。

癌细胞重新控制新陈代谢以维持高增殖率。除了糖酵解和谷氨酰胺分解以外，氨基酸还可以替代能源，补充脂肪酸的生物合成，并代表包括黑素瘤在内的转化细胞分泌蛋白的一部分。因此，我们研究了代表黑色素瘤细胞早期生长缓慢（WM35，WM278，WM793b和VM21）和快速转移（A375、518a2、6F和WM8）生长阶段的醋酸盐，丙酮酸和分泌蛋白的氨基酸组成，以鉴定这些配置文件中可能的信令组件。增殖测定和主成分分析显示，快速生长的黑色素瘤细胞与缓慢生长的黑色素瘤细胞之间存在严格的差异。此外，在抑制甲羟戊酸途径后，谷氨酸和丙氨酸被鉴定为条件培养基中的中心差异。补充谷氨酸的培养基以及与丙氨酸的组合可显着加速早期黑素瘤细胞的增殖，迁移和侵袭，但不能加速转移性细胞的增殖，迁移和侵袭。最后，对甲羟戊酸途径的抑制以时间依赖性方式消除了黑素瘤细胞的生长优势。综上所述，这些数据证实了生长和对细胞外谷氨酸和丙氨酸的侵袭性的阶段特异性反应，表明单个氨基酸的微环境信号传导。甲羟戊酸途径的抑制以时间依赖性方式消除了黑素瘤细胞的生长优势。综上所述，这些数据证实了生长和对细胞外谷氨酸和丙氨酸的侵袭性的阶段特异性反应，表明单个氨基酸的微环境信号传导。甲羟戊酸途径的抑制以时间依赖性方式消除了黑素瘤细胞的生长优势。综上所述，这些数据证实了生长和对细胞外谷氨酸和丙氨酸的侵袭性的阶段特异性反应，表明单个氨基酸的微环境信号传导。