M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3
Lamei Huang,
Fang Wang,
Xueping Wang,
Chaoyue Su,
Shaocong Wu,
Chuan Yang,
Min Luo,
Jianye Zhang,
Liwu Fu
Affiliations
Lamei Huang
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Fang Wang
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Xueping Wang
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Chaoyue Su
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou P. R. China
Shaocong Wu
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Chuan Yang
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Min Luo
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Jianye Zhang
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou P. R. China
Liwu Fu
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat‐sen University Cancer Center Guangzhou P. R. China
Abstract Metastasis is the most prevalent cause of cancer deaths, and immunological components of the tumor microenvironment, especially tumor‐associated macrophages (TAMs), play a vital role in cancer metastasis. However, the underlying mechanisms of TAMs on non‐small‐cell lung cancer (NSCLC) metastasis remain largely unexplored. Herein, we demonstrated that M2‐like TAMs facilitate the migration and invasion of cancer cells in vitro and in vivo through intercellular delivery of M2‐like macrophage‐derived exosomes (M2‐exos). Importantly, we found that M2‐exos had considerably higher levels of integrin (ITG) αV and β3. The impact of M2‐like macrophage‐mediated invasion and migration of NSCLC cells was clearly decreased when ITG αVβ3 was blocked. Mechanistically, exosomal ITG αVβ3 produced from M2‐like macrophages successfully triggered the focal adhesion kinase signaling pathway in recipient cells, boosting the migratory and invasive abilities of NSCLC cells. Clinically, we found that metastatic NSCLC patients had greater ITG αV and β3 expression, which was associated with a worse prognosis. This study reveals a novel mechanism by which M2‐exos significantly increased NSCLC cell migration and invasion by delivering integrin αVβ3. Exosomal ITG αVβ3 can be used as a potential prognostic marker, and blocking ITG αVβ3 could be a viable treatment option for preventing tumor metastasis.
