Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.
Department of Respiratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Cell Death Dis. 2019 May 16;10(6):377. doi: 10.1038/s41419-019-1618-x.
The mechanism by which tumor-associated macrophages (TAMs) affect cancer progression is not fully understood. This study developed a microfluidic-based co-culture device to mimic the tumor microenvironment to assess TAM effects on invasion and metastasis in NSCLC. The results showed lung carcinoma cells could cause macrophages to show the M2 (a TAM-like) phenotype, and these M2 macrophages promoted lung cancer cell EMT and invasion. Proteomic analysis by the iTRAQ quantitation strategy and GO ontology of the cancer cells indicated that αB-Crystallin (CRYAB) might be involved in this process. Further, we confirmed the role of CRYAB in cancer invasion and metastasis through cell and animal experiments, as well as human cancer tissue assessment. Overall, we demonstrated that M2 macrophages promote malignancy in lung cancer through the EMT by upregulating CRYAB expression and activating the ERK1/2/Fra-1/slug signaling pathway.
肿瘤相关巨噬细胞（TAMs）影响癌症进展的机制尚不完全清楚。本研究开发了一种基于微流控的共培养装置，以模拟肿瘤微环境，评估 TAM 对 NSCLC 侵袭和转移的影响。结果表明，肺癌细胞可使巨噬细胞呈现 M2（TAM 样）表型，这些 M2 巨噬细胞促进肺癌细胞 EMT 和侵袭。通过 iTRAQ 定量策略和癌症细胞的 GO 本体分析的蛋白质组学分析表明，αB-晶状体蛋白（CRYAB）可能参与了这一过程。此外，我们通过细胞和动物实验以及人类癌症组织评估，证实了 CRYAB 在癌症侵袭和转移中的作用。总的来说，我们证明了 M2 巨噬细胞通过上调 CRYAB 表达并激活 ERK1/2/Fra-1/slug 信号通路，通过 EMT 促进肺癌的恶性转化。
