Tumor Biology

, Volume 35, Issue 6, pp 6105–6111 | Cite as

Tumor-associated mesothelial cells are negative prognostic factors in gastric cancer and promote peritoneal dissemination of adherent gastric cancer cells by chemotaxis

  • Zhi-Feng Miao
  • Ting-Ting Zhao
  • Zhen-Ning Wang
  • Feng Miao
  • Ying-Ying Xu
  • Xiao-Yun Mao
  • Jian Gao
  • Hui-Mian Xu
Research Article


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.


Peritoneal carcinomatosis Stomach cancer Tumor-associated human peritoneal mesothelial cell Prognosis Fibrotic disease 



We thank Prof. Feng Li for the excellent technical guidance and assistance. This work was support by the National Science Foundation of China (no. 81272718 and no. 81302125)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Zhi-Feng Miao
    • 1
  • Ting-Ting Zhao
    • 2
  • Zhen-Ning Wang
    • 1
  • Feng Miao
    • 3
  • Ying-Ying Xu
    • 2
  • Xiao-Yun Mao
    • 2
  • Jian Gao
    • 4
  • Hui-Mian Xu
    • 1
  1. 1.Department of Surgical OncologyThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Breast SurgeryThe First Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Department of DigestionThe Fourth Affiliated Hospital of China Medical UniversityShenyangChina
  4. 4.Center of Laboratory Technology and Experimental MedicineChina Medical UniversityShenyangChina

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