背景：在发育过程中，胚胎采用不同的策略来清除不需要的细胞。通过类似于胚胎细胞的一些程序，我们从外周血单个核细胞(PBMCs)中，产生了抗肿瘤的条件培养基 (CM)，该CM是由抑制AMPK的淋巴细胞和单核细胞生成的。方法：应用药理剂Dorsomorphin来抑制AMPK信号，评估其条件培养基(CM)在体外细胞培养、乳腺癌组织和乳腺肿瘤和肿瘤引起的骨质疏松症的小鼠模型中的治疗效果。利用基于质谱的蛋白质组学、Western blotting、免疫沉淀、基因过表达和RNA干扰评估其调节机制。结果：虽然AMPK信号通路主要具有抗肿瘤作用，但我们用其抑制方法制造了诱导性的抑肿瘤细胞和它们的抗肿瘤CM。在乳腺癌小鼠模型中，抑制AMPK的淋巴细胞衍生的CM使乳腺肿瘤的减少量比化疗剂Taxol更强效，在肿瘤携带的胫骨中也防止了骨质流失。此外，从同一患者分离出的外周血CM降低了同一患者的人体乳腺癌的外体组织的体外增殖。值得注意的是，CM中富含的蛋白质包括在许多类型的肿瘤中被认为具有致癌作用的Moesin (MSN)、烯醇酶1(ENO1)和多A结合蛋白1(PABPC1)。MSN和ENO1的肿瘤抑制作用至少在一定程度上是由已知促进转移的Metadherin (Mtdh)介导的。结论：我们证明PBMCs可用于生成抗肿瘤蛋白质组，把外泌的抗肿瘤蛋白质如MSN、ENO1和PABPC1，从致癌因子转化而来。结果支持开发自体血源疗法的可能性，通过抑制AMPK信号在工程PBMC衍生的CM中富集抗肿瘤蛋白质。©作者。

Background: During a developmental process, embryos employ varying tactics to remove unwanted cells. Using a procedure analogous to some of the embryonic cells, we generated a tumor-eliminating conditioned medium (CM) from AMPK-inhibited lymphocytes and monocytes in peripheral blood mononuclear cells (PBMCs). Methods: AMPK signaling was inhibited by the application of a pharmacological agent, Dorsomorphin, and the therapeutic effects of their conditioned medium (CM) were evaluated using in vitro cell cultures, ex vivo breast cancer tissues, and a mouse model of mammary tumors and tumor-induced osteolysis. The regulatory mechanism was evaluated using mass spectrometry-based proteomics, Western blotting, immunoprecipitation, gene overexpression, and RNA interference. Results: While AMPK signaling acted mostly anti-tumorigenic, we paradoxically inhibited it to build induced tumor-suppressing cells and their tumor-eliminating CM. In a mouse model of breast cancer, the application of AMPK-inhibited lymphocyte-derived CM reduced mammary tumors additively to a chemotherapeutic agent, Taxol. It also prevented bone loss in the tumor-bearing tibia. Furthermore, the application of CM from the patient-derived peripheral blood diminished ex vivo breast cancer tissues isolated from the same patients. Notably, proteins enriched in CM included Moesin (MSN), Enolase 1 (ENO1), and polyA-binding protein 1 (PABPC1), which are considered tumorigenic in many types of cancer. The tumor-suppressing actions of MSN and ENO1 were at least in part mediated by Metadherin (Mtdh), which is known to promote metastatic seeding. Conclusion: We demonstrated that PBMCs can be used to generate tumor-suppressive proteomes, and extracellular tumor-suppressing proteins such as MSN, ENO1, and PABPC1 are converted from tumor-promoting factors inside cancer cells. The results support the possibility of developing autologous blood-based therapy, in which tumor-suppressing proteins are enriched in engineered PBMC-derived CM by the inhibition of AMPK signaling.© The author(s).