Institut de Génétique Moléculaire de Montpellier IGMM, CNRS, Montpellier, France.
Lab Invest. 2013 May;93(5):611-21. doi: 10.1038/labinvest.2013.44. Epub 2013 Mar 4.
Metabolic adaptations and changes in the expression of nutrient transporters are known to accompany tumorigenic processes. Nevertheless, in the context of solid tumors, studies of metabolism are hindered by a paucity of tools allowing the identification of cell surface transporters on individual cells. Here, we developed a method for the dissociation of human breast cancer tumor xenografts combined with quantification of cell surface markers, including metabolite transporters. The expression profiles of four relevant nutrient transporters for cancer cells' metabolism, Glut1, ASCT2, PiT1 and PiT2 (participating to glucose, glutamine and inorganic phosphate, respectively), as detected by new retroviral envelope glycoprotein-derived ligands, were distinctive of each tumor, unveiling underlying differences in metabolic pathways. Our tumor dissociation procedure and nutrient transporter profiling technology provides opportunities for future basic research, clinical diagnosis, prognosis and evaluation of therapeutic responses, as well as for drug discovery and development.
代谢适应和营养转运体表达的变化伴随着肿瘤发生过程。然而,在实体瘤的背景下,由于缺乏能够鉴定单个细胞表面转运体的工具,对代谢的研究受到了阻碍。在这里,我们开发了一种分离人乳腺癌肿瘤异种移植物的方法,并结合了细胞表面标志物的定量分析,包括代谢物转运体。通过新的逆转录病毒包膜糖蛋白衍生配体检测到四种与癌细胞代谢相关的营养转运体(Glut1、ASCT2、PiT1 和 PiT2,分别参与葡萄糖、谷氨酰胺和无机磷酸盐的转运)的表达谱在每个肿瘤中都是独特的,揭示了代谢途径的潜在差异。我们的肿瘤分离程序和营养转运体分析技术为未来的基础研究、临床诊断、预后和治疗反应评估以及药物发现和开发提供了机会。