title: CD97 promotion of gastric carcinoma lymphatic metastasis is exosome dependent.
abstract: BACKGROUND
  CD97 knockdown impairs the metastatic capacity of SGC-7901 gastric cancer cells. However, the role of CD97 in the distant lymphatic premetastatic niche formation of gastric cancer remains unknown.
  
  
  METHODS
  Exosomes and the soluble fraction were isolated from SGC-L (an SGC-7901-cell-derived highly lymphatic metastatic cell line) and CD97-knockdown (SGC-L/CD97-kd) cells, and were co-cultured with gastric cancer cells. The metastatic capacity of the two cell lines was evaluated in vitro and in a footpad lymph node metastasis mouse model. Premetastatic-niche-formation-related proteins were examined immunohistochemically.
  
  
  RESULTS
  CD97 expression was ninefold higher in SGC-L cells than in SGC-7901 cells. In vitro, exosomes or conditioned medium from the SGC-L cells enhanced cell proliferation (20 % increase) and invasion (30 % increase) as compared with that from SGC-L/CD97-kd cells (p < 0.01). Intrafootpad injections of SGC-L, but not SGC-L/CD97-kd exosomes or conditioned medium, strongly promoted SGC-L and SGC-L/CD97-kd cell accumulation in the draining lymph nodes (p < 0.01) and increased CD55, CD44v6, α5β1, CD31, epithelial cell adhesion molecule, and CD151 expression. Although the SGC-L/CD97-kd exosomes alone were insufficient for promotion of metastasis, they were partly aided by the SGC-L-cell-derived soluble fraction.
  
  
  CONCLUSIONS
  The CD97 small isoform promotes SGC-L cell lymphatic metastasis exosome dependently, and aided by the soluble fraction, the exosome-dependent CD97 plays a pivotal role in premetastatic niche formation.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Daren
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Research Lab, Department of Internal Medicine II, Halle (Saale) University Hospital, Halle (Saale), Germany.
authors.forename: Bogusz
authors.initials: B
authors.lastname: Trojanowicz
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Dike
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Chenni
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China.
authors.forename: Zhefang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou, 310009, People's Republic of China. chenli@mail.hz.zj.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D055354:Exosomes / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D035683:MicroRNAs; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: CD97; Exosomes; Gastric cancer; Lymphatic metastasis