Metabolites in the tumor microenvironment are a critical factor for tumor progression. However, the lack of knowledge about the metabolic profile in the bone marrow (BM) microenvironment of multiple myeloma (MM) limits our understanding of MM progression. Here, we show that the glycine concentration in the BM microenvironment is elevated due to bone collagen degradation mediated by MM cell-secreted matrix metallopeptidase 13 (MMP13), while the elevated glycine level is linked to MM progression. MM cells utilize the channel protein solute carrier family 6 member 9 (SLC6A9) to absorb extrinsic glycine subsequently involved in the synthesis of glutathione (GSH) and purines. Inhibiting glycine utilization via SLC6A9 knockdown or the treatment with betaine suppresses MM cell proliferation and enhances the effects of bortezomib on MM cells. Together, we identify glycine as a key metabolic regulator of MM, unveil molecular mechanisms governing MM progression, and provide a promising therapeutic strategy for MM treatment.

肿瘤微环境中的代谢物是肿瘤进展的关键因素。然而，缺乏对多发性骨髓瘤 (MM) 骨髓 (BM) 微环境中代谢谱的了解限制了我们对 MM 进展的理解。在这里，我们显示 BM 微环境中的甘氨酸浓度升高是由于 MM 细胞分泌的基质金属肽酶 13 (MMP13) 介导的骨胶原降解，而升高的甘氨酸水平与 MM 进展有关。MM 细胞利用通道蛋白溶质载体家族 6 成员 9 (SLC6A9) 吸收外源甘氨酸，随后参与谷胱甘肽 (GSH) 和嘌呤的合成。通过 SLC6A9 敲低或甜菜碱处理抑制甘氨酸利用可抑制 MM 细胞增殖并增强硼替佐米对 MM 细胞的作用。一起，