The significance of the co-existence of osteopontin and tumor-associated macrophages in gastric cancer progression

BMC Cancer. 2015 Mar 15;15:128. doi: 10.1186/s12885-015-1114-3.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Disease Progression
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism*
  • Macrophages / pathology*
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Staging
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • Paracrine Communication
  • Prognosis
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Tumor Burden


  • Biomarkers, Tumor
  • MSR1 protein, human
  • Scavenger Receptors, Class A
  • Osteopontin