title: Tumor-associated mesothelial cells are negative prognostic factors in gastric cancer and promote peritoneal dissemination of adherent gastric cancer cells by chemotaxis.
abstract: Peritoneal dissemination is highly frequent in gastric cancer. Damage to human peritoneal mesothelial cell (HPMC) barriers provokes gastric cancer peritoneal dissemination (GCPD), the key events during GCPD, is characterized by fibroblastic development. In this study, we have studied the association between fibroblast activation protein (FAP) expression in peritoneum and the pathological features of the primary tumor. The clinical prognosis of gastric cancer patients was evaluated according to FAP expression. In a gastric cancer cell-HPMC co-culture system, expression of E-cadherin, α-smooth muscle actin, and FAP were evaluated by Western blotting. Gastric cancer cell migration and adhesion to HPMC were also assayed. Our results showed positive peritoneal staining of FAP in 36/86 cases (41.9 %), which was associated with a higher TNM stage in primary gastric cancer and higher incidence of GCPD (both p<0.05). Survival analysis showed FAP expression was an independent prognostic factor of poor survival (p=0.02). Peritoneum of FAP-positive expression exhibited a distinct fibrotic development and expressed higher level of the mesenchymal marker α-SMA, which was confirmed by the in vitro Western blot assay. In HPMC and gastric cancer cell adherence assay, SGC-7901 cells preferentially adhered to TA-HPMC at different cell densities (both p<0.05). Additionally, SGC-7901 cells were more prone to chemotaxis by FAP-expressed tumor-associated-human peritoneal mesothelial cells (TA-HPMC) compared with HPMC co-cultured with normal gastric glandular epithelial cells in a time-dependent manner (both p<0.05). Our study indicated a positive correlation between peritoneum FAP expression and GCPD. FAP-expressed TA-HPMC might be an important cellular component and instigator of GCPD.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning Province, China, 110001.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Miao
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Miao
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Mao
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
mesh_terms: D002633:Chemotaxis; D010450:Endopeptidases; D004847:Epithelial Cells / Q000502:physiology*; D005355:Fibrosis; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D010537:Peritoneum / Q000473:pathology*; D011379:Prognosis; D012697:Serine Endopeptidases / Q000032:analysis; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha