JAM-C promotes lymphangiogenesis and nodal metastasis in non-small cell lung cancer

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• 作者：SongNan Hao (1) (2)
  YanMei Yang (3)
  Yan Liu (4)
  ShuCai Yang (1)
  Geng Wang (1)
  JianBing Xiao (1)
  HuiDong Liu (1)
  
• 关键词：Lung carcinomas ; JAM ; C ; Lymphangiogenesis ; Metastasis ; Survival
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：35
• 期：6
• 页码：5675-5687
• 全文大小：
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• 作者单位：SongNan Hao (1) (2)
  YanMei Yang (3)
  Yan Liu (4)
  ShuCai Yang (1)
  Geng Wang (1)
  JianBing Xiao (1)
  HuiDong Liu (1)
  
  1. Department of Anatomy, Harbin Medical University, 194 Xue-fu Road, Harbin, Heilongjiang, 150081, China
  2. Department of Orthopedics, Harbin Fifth Hospital, Harbin, Heilongjiang, 150040, China
  3. Cancer Institute, Harbin Medical University, Harbin, Heilongjiang, 150081, China
  4. Department of General Surgery, The Affiliated Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang, 157011, China
  
• ISSN：1423-0380

文摘

This study aims to investigate lymphatic metastasis-related genes in non-small cell lung carcinomas (NSCLC). NSCLC tissue was analyzed for expression of junctional adhesion molecule-C (JAM-C) protein. Our data revealed novel associations between JAM-C overexpression in primary tumors and lymphatic microvessel density (LMVD), lymph node metastasis, and poorer overall survival and recurrence-free survival. We used the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, in vivo and vitro. We found that JAM-C played an important role in different metastasis capacity of lymph node. JAM-C affected tumor growth, LNM, JAM-C, VEGF-C, vasculature, and ERK1/2 phosphorylation (p-ERK1/2). β1 integrin was involved in lymph node metastasis. Moreover, JAM-C knockdown in highly metastatic Anip973 decreased cell migration in scratch-wound assays. The JAM-C knockdown in Anip973 cells and JAM-C cDNA in AGZY83-a cells regulated the vascular endothelial growth factor C (VEGF-C) expression. Immunofluorescence showed that blocked VEGF-C expression in JAM-C shRNA Anip973 cells were restored after JAM-C treatment. JAM-C-induced VEGF-C in JAM-C cDNA AGZY83-a cells was also effectively inhibited by treatment with an antibody specifically against JAM-C. Use of media from Anip973 cells, AGZY83-a, and A549cells lung cancer cells that overexpressed or downregulated JAM-C was demonstrated to affect activity of VEGF-C-induced β1 integrin subunit or ERK activity in human dermal lymphatic endothelial cells (HDLEC) treated with VEGF-C or inhibitory antibody to JAM-C. Overall, these results indicate that JAM-C could mediate metastasis as it contributes to VEGF-C expression in cancer cells. JAM-C affects β1and ERK activation in HDLEC, thus promoting lymphangiogenesis and nodal metastasis. Our findings indicate that JAM-C may be a therapeutic target for preventing and treating lymphatic metastases.