间充质干细胞通过分解代谢糖酵解促进肺癌细胞生长（英文）

Mesenchymal Stem Cells Promote Growth of Lung Cancer Cells Through Catabolic Glycolysis

存在于骨髓中的间充质干细胞(bone marrow mesenchymal stem cells,BMSCs,也称为间充质基质细胞)可以被募集到肿瘤部位并构成肿瘤微环境。细胞代谢在癌症进展中起重要作用。在癌症微环境中间充质细胞和肿瘤细胞发生代谢方式的转变。然而,尚不清楚肿瘤细胞和BMSCs细胞的相互作用如何影响细胞代谢和肿瘤进展。在本研究中,通过将BMSCs和小鼠肺癌细胞LLC细胞共同注射到C57BL/6小鼠,构建了皮下瘤模型;随后在原位瘤分离BMSCs和LLC细胞,进行RNA测序,以获得肿瘤微环境下BMSCs和LLC细胞的转录组。结果显示BMSCs中上调的基因富集于代谢途径。进一步根据差异表达的分子构建相互作用网路,发现BMSCs网络中的核心预测途径是代谢途径、MAPK信号通路和HIF-1信号通路。然而,在肿瘤微环境中LLC细胞的代谢途径受到抑制。体内动物实验证实抑制糖酵解可以减少荷瘤小鼠肿瘤的生长。以上结果提示,BMSCs增加了糖酵解,通过反式Warburg效应促进癌细胞的生长,在肿瘤微环境下BMSCs的代谢重编程影响肿瘤细胞的转归。

Mesenchymal stem/stromal cells(MSCs),which reside mainly in bone marrow,are known to be re-cruited to tumor sites and constitute the tumor microenvironment.Metabolism plays an important role in cancer progression.In the cancer microenvironment,cells including mesenchymal and cancer cells have a shift between glycolysis and mitochondrial oxidative phosphorylation.However,how the interaction of cancer cells and bone marrow MSCs(BMSCs)affects the metabolism of cells and cancer progression remains to be elucidated.Herein,an animal model was established by subcutaneously co-injecting BMSCs and murine Lewis lung cancer(LLC)cells into C57 BL/6 mice.BMSCs and LLC cells were isolated from primary tumor sites,and RNA sequencing was performed to obtain the transcriptomic profiles in BMSCs and LLC cells under the cancer microenvironment.The result revealed that the upregulated genes in BMSCs were enriched in the metabolic pathway.The Pathway-Act-Network was built according to differentially expressed molecules,and the results showed that the core predicted pathways in the network of BMSCs were metabolic pathways,MAPK signaling pathway and HIF-1 signaling pathway.However,the metabolic pathways were suppressed in LLC cells in cancer microenvironment.Inhibition of glycolysis could reduce the tumor growth in vivo.The study concluded that BMSCs increase glycolysis,promoting growth of cancer cells through reverse Warburg effect.Metabolic reprogramming of BMSCs in cancer microenvironment would determine the fate of cancer cells.