Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters

优化肿瘤异种移植解离以分析细胞表面标志物和营养转运蛋白

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作者:Vincent Petit, Gérald Massonnet, Zofia Maciorowski, Jawida Touhami, Aurélie Thuleau, Fariba Némati, Julie Laval, Sophie Château-Joubert, Jean-Luc Servely, David Vallerand, Jean-Jacques Fontaine, Naomi Taylor, Jean-Luc Battini, Marc Sitbon, Didier Decaudin

Abstract

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.

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