Tumor hypoxia enhances Non-Small Cell Lung Cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling
Evidence has been proposed tumor-associated macrophages (TAMs) are participated in the prognosis of tumor.Though hypoxia has been proved to play a prominent role in the infiltration of TAMs into tumor tissue,the impact of hypoxia on the TAMs phenotype shift and functional responses remains enigmatic.In the present study,we observe CD209+ macrophage (Mφ) infiltration is associated with the tumor metastasis in human adenocarcinoma Non-Small Cell Lung Cancer (NSCLC).By applying the in vivo hypoxia tumor model,our results further show that intermittent hypoxia significantly promotes the metastasis rate of Lewis lung carcinoma (LLC), accompanied with more CD209+ TAMs infiltrated in primary tumor tissue,suggesting M2 TAMs might have a profound influence on hypoxia-mediated LLC metastasis in vivo.More intriguingly,by skewing Mφ polarization away from the M1-to a tumor-promoting M2-like phenotype, hypoxia and IL-6 cooperate to enhance the LLC metastasis both in vitro and in vivo.In addition,we also demonstrate that skewing of Mφ M2 polarization by hypoxia relies substantially on activation of ERK signaling.Collectively, these observations unveil a novel tumor hypoxia concept involving the TAM phenotype shift and highlight the potential of reeducation of TAM polarization in anticancer treatment.
TAMs Hypoxia Metastasis Polarization
Jun Zhang Ji Cao Rong Dong Meidan Ying Qinjie Weng Jian Ma Qiaojun He Bo Yang
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,Institute of Pharmacology and Toxicology,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,China,310058
国内会议
杭州
英文
97-114
2013-10-01（万方平台首次上网日期，不代表论文的发表时间）