title: Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro.
abstract: BACKGROUND
  CXCR1 and CXCR2, cell surface receptors of interleukin-8, regulate cell migration and alteration of their expression has been associated with poor prognosis of various cancers. The aim of this study was to detect their expression in gastric cancer to identify associations with another cell adhesion molecule, matrix metalloproteinase-9 (MMP9), and with clinicopathological data ex vivo, and then explore their potential role in gastric cancer cells in vitro.
  
  
  METHODS
  A total of 172 cases of gastric cancer tissue specimens were collected for immunohistochemical analysis of CXCR1, CXCR2, and MMP9 expression. Expression of CXCR1 and CXCR2 proteins was knocked in or down using their cDNA and shRNA, respectively, in gastric cancer cell lines to assess the changed cell phenotypes and gene expression.
  
  
  RESULTS
  CXCR1, CXCR2, and MMP9 were expressed in 61.0%, 77.9%, and 75.6% of gastric cancer tissues, respectively. Moreover, CXCR1 and CXCR2 expression was associated with tumor differentiations, advanced clinical stages, lymph node, and distant metastasis of gastric cancer. Similarly, MMP9 expression was associated with CXCR1 and CXCR2. Expression of these three proteins was interrelated. In vitro study showed that levels of CXCR1 and CXCR2 proteins were associated with the capacity of gastric cancer cell migration, while knockdown of their expression inhibited gastric cancer cell migration and invasion abilities in vitro. In contrast, overexpression of CXCR1 and CXCR2 proteins promoted tumor cell migration and invasion. At the gene levels, knockdown of CXCR1 or CXCR2 expression suppressed expression of Ets-1, SRC-1, and JNK proteins and phosphorylated c-Jun and Erk1/2. Conversely, upregulation of CXCR1 or CXCR2 promoted expression of Ets-1, SRC-1, JNK, and c-Jun proteins and phosphorylated JNK, c-Jun and Erk1/2.
  
  
  CONCLUSIONS
  These findings suggest that CXCR1 and CXCR2 play an important role in gastric cancer progression. Further study will be performed to investigate whether target of their expression can be used as a novel strategy in clinical control of gastric cancer metastasis.
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Suiwei
authors.initials: S
authors.lastname: Dong
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Ge
authors.affiliation: Department of Osteology, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Ruilei
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Osteology, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Cancer Biotherapy Center, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China. Electronic address: songxin68@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of General Surgery, Tumor Hospital of Yunnan Province Affiliated to Kunming Medical University, Kunming, Yunnan, China. Electronic address: kmtjing@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D056920:Nuclear Receptor Coactivator 1 / Q000096:biosynthesis; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis* / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
chemical_list: C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: CXCR1; CXCR2; Cancer metastasis; Gastric cancer; MMP9