title: Blocking TGF-β1 by P17 peptides attenuates gastric cancer cell induced peritoneal fibrosis and prevents peritoneal dissemination in vitro and in vivo.
abstract: Our previous study demonstrated that the peritoneal stroma environment favors proliferation of tumor cells by serving as a rich source of growth factors and chemokines known to be involved in tumor metastasis. In this study, we investigated the interaction between gastric cancer cells and peritoneal mesothelial cells, and determined the effects of TGF-β1 in this processing. Human peritoneal tissues and peritoneal wash fluid were obtained, which examined by hematoxylin and eosin staining or ELISA for measurements of TGF-β1 levels. The peritoneal mesothelial cells were co-incubated with the supernatants of gastric cancer, the expression of TGF-β1, collagen and fibronectin was observed by ELISA and western blot. We then investigated the effects of serum-free conditioned media from HSC-39 gastric cancer cells on the peritoneum of nude mice, and the effects of peritoneal fibrosis on the development of peritoneal metastasis in vivo. The peritoneum from gastric patients were thickened and contained extensive fibrosis. After co-culture both gastric tumor cells and mesothelial cells, we found that TGF-β1 expression was greatly increased in the co-culture system compared to individual culture condition. Serum-free Conditioned Media from HSC-39 was able to induce extracellular matrix expression in vitro and in vivo, and tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum, while blocking TGF-β1 by peptide P17 can partially inhibit these effects. In conclusion, these results indicated that the interaction of gastric cancer with peritoneal fibrosis and determined that TGF-β1 plays a key role in induction of peritoneal fibrosis, which in turn affected dissemination of gastric cancer.
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China; Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001, PR China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Lv
authors.affiliation: Department of General Surgery, The Affiliated Hospital of Chifeng University, Chifeng 024000, PR China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Zhao
authors.affiliation: Cerebrovascular Disease Research Institute and (e)Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Jin
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: Departments of Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001, PR China. Electronic address: xuhuimianpf@163.com.
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. Electronic address: qingyiwhb@126.com.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010533:Peritoneal Lavage; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000150:complications* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024061:Collagen Type III; D005353:Fibronectins; C562050:P17 peptide; D010455:Peptides; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: Extracellular matrix; Mesothelial cell; Peritoneal carcinomatosis; Stomach cancer; TGF-β1