title: Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8.
abstract: BACKGROUND
  Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with tumor growth and progression. However, the roles of tumor-resident MSCs in cancer have not been thoroughly clarified. This study was to investigate the regulating effect of gastric cancer-derived MSCs (GC-MSCs) on gastric cancer and elucidate the underlying mechanism.
  
  
  METHODS
  GC-MSCs were isolated from primary human gastric cancer tissues and characterized. The effect of GC-MSCs on gastric cancer cell proliferation was analyzed by MTT assay and colony formation assay. Transwell migration assay was performed to evaluate the influence of GC-MSCs in gastric cancer cell migration. The regulating effects of interactions between gastric cancer cells and GC-MSCs on their pro-angiogenic abilities were analyzed in a co-culture system, with the expression, and secretion of pro-angiogenic factors detected by RT-PCR and Luminex assay. Tube formation assay was used to further validate the angiogenic capability of gastric cancer cells or GC-MSCs. Cytokine profiles in the supernatant of GC-MSCs were screened by Luminex assay and neutralizing antibody was used to identify the key effective cytokines. The activations of Akt and Erk1/2 in gastric caner cells were detected by Western blot.
  
  
  RESULTS
  GC-MSC treatment enhanced the proliferation and migration of BGC-823 and MKN-28 cells, which was more potently than MSCs from adjacent non-cancerous tissues (GCN-MSCs) or bone marrow (BM-MSCs). Higher expression levels of pro-angiogenic factors were detected in GC-MSCs than GCN-MSCs or BM-MSCs. After 10 % GC-MSC-CM treatment, BGC-823, and MKN-28 cells expressed increased levels of pro-angiogenic factors and facilitated tube formation more potently than cancer cells alone. Furthermore, GC-MSCs produced an extremely higher level of interleukin-8 (IL-8) than GCN-MSCs or BM-MSCs. Blockade of IL-8 by neutralizing antibody significantly attenuated the tumor-promoting effect of GC-MSCs. In addition, 10 % CM of IL-8-secreted GC-MSCs induced the activations of Akt or Erk1/2 pathway in BGC-823 and MKN-28 cells.
  
  
  CONCLUSIONS
  Tumor-resident GC-MSCs promote gastric cancer growth and progression more efficiently than GCN-MSCs or BM-MSCs through a considerable secretion of IL-8, which could be a possible target for gastric cancer therapy.
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. medical112@126.com.|Department of Pathology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, China. medical112@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. zhouying0524@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. yangjinseu@yahoo.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, China. xuzhang@ujs.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. zhhh2027@163.com.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. ttz0823@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. zhaoshaolin1@163.com.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. zp099@sohu.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. huyongli@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Huo
authors.affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. lygwuhuiyi@163.com.
authors.forename: Huiyi
authors.initials: H
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation / Q000379:methods; D017077:Culture Media, Conditioned / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D016130:Immunophenotyping; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8