Extracellular vesicles promotes liver metastasis of lung cancer by ALAHM increasing hepatocellular secretion of HGF

Chunyang Jiang; Xu Li; Bingsheng Sun; Na Zhang; Jing Li; Shijing Yue; Xiaoli Hu

doi:10.1016/j.isci.2022.103984

Extracellular vesicles promotes liver metastasis of lung cancer by ALAHM increasing hepatocellular secretion of HGF

iScience. 2022 Feb 24;25(3):103984. doi: 10.1016/j.isci.2022.103984. eCollection 2022 Mar 18.

Authors

Chunyang Jiang¹, Xu Li², Bingsheng Sun³, Na Zhang⁴, Jing Li⁴, Shijing Yue⁵, Xiaoli Hu⁶

Affiliations

¹ Department of Thoracic Surgery, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin, China.
² Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
³ Department of Thoracic Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, Tianjin, China.
⁴ Department of Respiratory Medicine, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin, China.
⁵ The State Key Laboratory of Medicinal Chemical Biology, School of Medicine, The State International Science & Technology Cooperation Base of Tumor Immunology and Biological Vaccines, Nankai University, 94 Weijin Road, Nankai District, Tianjin 300071, Tianjin, China.
⁶ Department of Respiratory Medicine, The Second People'|'s Hospital of Linhai City, 198 Dubei Road, Linhai 317016, Zhejiang Province, China.

Abstract

Tumor-derived extracellular vesicles (EVs) are involved in tumor metastasis. Highly enriched lncRNA-ALAHM was identified from serum EVs of lung adenocarcinoma (LUAD) patients with liver metastasis by high-throughput sequencing. A mouse model of in situ lung cancer was used to determine the effect of ALAHM in LUAD cell EVs on liver metastasis. The effects of ALAHM on hepatocyte paracrine HGF as well as proliferation, invasion, and migration of LUAD cells were observed in vitro. As results, ALAHM expression in LUAD cell EVs was significantly increased. LUAD-cell-derived EVs overexpressing ALAHM significantly promoted lung cancer liver metastasis in model mice. ALAHM of LUAD cell EVs also promotes hepatocyte parasecretion of HGF by binding with AUF1 and increases the proliferation, invasion, and migration of LUAD cells. Thus, LUAD-cell-derived EVs containing ALAHM causes increasing HGF and promoting liver metastasis of LUAD cells.

Keywords: Cancer; Microenvironment; Molecular biology.