title: The significance of the co-existence of osteopontin and tumor-associated macrophages in gastric cancer progression.
abstract: BACKGROUND
  Osteopontin (OPN) can recruit macrophages to the site of inflammation and promote tumorigenesis. M2 tumor-associated macrophages (M2-TAMs) also play an important role in cancer progression. This study aimed to clarify the role of OPN and M2-TAMs co-existence in gastric cancer.
  
  
  METHODS
  The levels of OPN and M2-TAMs were evaluated by immunohistochemical staining in 170 resected gastric cancer specimens that were collected from 1998 to 2012. M2-TAMs were identified by staining for an M2 marker, CD204. The prognostic significance and correlation between OPN and CD204 expression were analyzed. A co-culture system of OPN+-AGS and U937 cells was designed to study the effect of OPN on the skewing of macrophages toward M2-TAMs for gastric cancer progression in vitro and in vivo.
  
  
  RESULTS
  Patients with high expression (>50%) of OPN or CD204 exhibited poor 5-year overall survival rates (48.61%, p = 0.0055, and 52.14%, p = 0.0498, respectively). A positive correlation was observed between OPN and CD204 expression and high co-expression of OPN and CD204 demonstrated poor 5-year overall survival rates (48.90%, p = 0.0131). In the co-culture study, OPN was able to attract U937 cells and skew them toward M2-TAMs through paracrine action. The M2-TAMs could increase the invasiveness of OPN+-AGS cells and the growth rate of xenograft of a mixture of co-cultured OPN+-AGS and U937 cells.
  
  
  CONCLUSIONS
  OPN can skew macrophages toward M2-TAMs during gastric cancer progression. The co-existence of OPN and infiltrating M2-TAMs correlates with disease progression and poor survival and thus can serve as a prognostic marker in gastric cancer.
authors: Chang-Ni
authors: CN
authors: Lin
authors: Chih-Jung
authors: CJ
authors: Wang
authors: Ying-Jui
authors: YJ
authors: Chao
authors: Ming-Derg
authors: MD
authors: Lai
authors: Yan-Shen
authors: YS
authors: Shan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D019899:Paracrine Communication; D011379:Prognosis; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A; D053495:Osteopontin