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

Lin CN, Wang CJ, Chao YJ, Lai MD, Shan YS - BMC Cancer (2015)

Bottom Line: M2 tumor-associated macrophages (M2-TAMs) also play an important role in cancer progression.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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Receiver operating characteristic (ROC) curves for the tumor size, tumor stage, lymph node metastasis, and co-expression of OPN and CD204 were used to predict overall gastric cancer survival. The area under the ROC curve for tumor size was 0.624 (95% CI, 0.540-0.709), tumor stage was 0.710 (95% CI, 0.630-0.789), lymph node metastasis was 0.663 (95% CI, 0.581-0.745), and co-expression of OPN and CD204 was 0.637 (95% CI, 0.554-0.720). These parameters were significantly associated with overall survival (p = 0.005, 0.000, 0.000, and 0.002).
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Fig2: Receiver operating characteristic (ROC) curves for the tumor size, tumor stage, lymph node metastasis, and co-expression of OPN and CD204 were used to predict overall gastric cancer survival. The area under the ROC curve for tumor size was 0.624 (95% CI, 0.540-0.709), tumor stage was 0.710 (95% CI, 0.630-0.789), lymph node metastasis was 0.663 (95% CI, 0.581-0.745), and co-expression of OPN and CD204 was 0.637 (95% CI, 0.554-0.720). These parameters were significantly associated with overall survival (p = 0.005, 0.000, 0.000, and 0.002).

Mentions: In univariate and multivariate analysis, the tumor size, tumor stage, lymph node metastasis, OPN expression, and CD204 expression were significantly associated with overall survival of patients with gastric cancer (Table 2). Notably, the co-expression of OPN and CD204 was more significantly associated with overall survival (p < 0.01) compared with OPN (p < 0.05) or CD204 (p < 0.05) alone. To confirm the correlation between the co-expression of OPN and CD204 and overall survival, ROC curve analysis was used. We found that the co-expression of OPN and CD204 was highly associated with overall survival. The tumor size (p = 0.005), tumor stage (p = 0.000), lymph node metastasis (p = 0.000), and co-expression of OPN and CD204 (p = 0.002) were significantly associated with the overall outcome (Figure 2). The results demonstrated that the co-existence of OPN and M2-TAMs in gastric cancer was highly associated with the overall survival of gastric cancer patients.Table 2


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

Lin CN, Wang CJ, Chao YJ, Lai MD, Shan YS - BMC Cancer (2015)

Receiver operating characteristic (ROC) curves for the tumor size, tumor stage, lymph node metastasis, and co-expression of OPN and CD204 were used to predict overall gastric cancer survival. The area under the ROC curve for tumor size was 0.624 (95% CI, 0.540-0.709), tumor stage was 0.710 (95% CI, 0.630-0.789), lymph node metastasis was 0.663 (95% CI, 0.581-0.745), and co-expression of OPN and CD204 was 0.637 (95% CI, 0.554-0.720). These parameters were significantly associated with overall survival (p = 0.005, 0.000, 0.000, and 0.002).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384326&req=5

Fig2: Receiver operating characteristic (ROC) curves for the tumor size, tumor stage, lymph node metastasis, and co-expression of OPN and CD204 were used to predict overall gastric cancer survival. The area under the ROC curve for tumor size was 0.624 (95% CI, 0.540-0.709), tumor stage was 0.710 (95% CI, 0.630-0.789), lymph node metastasis was 0.663 (95% CI, 0.581-0.745), and co-expression of OPN and CD204 was 0.637 (95% CI, 0.554-0.720). These parameters were significantly associated with overall survival (p = 0.005, 0.000, 0.000, and 0.002).
Mentions: In univariate and multivariate analysis, the tumor size, tumor stage, lymph node metastasis, OPN expression, and CD204 expression were significantly associated with overall survival of patients with gastric cancer (Table 2). Notably, the co-expression of OPN and CD204 was more significantly associated with overall survival (p < 0.01) compared with OPN (p < 0.05) or CD204 (p < 0.05) alone. To confirm the correlation between the co-expression of OPN and CD204 and overall survival, ROC curve analysis was used. We found that the co-expression of OPN and CD204 was highly associated with overall survival. The tumor size (p = 0.005), tumor stage (p = 0.000), lymph node metastasis (p = 0.000), and co-expression of OPN and CD204 (p = 0.002) were significantly associated with the overall outcome (Figure 2). The results demonstrated that the co-existence of OPN and M2-TAMs in gastric cancer was highly associated with the overall survival of gastric cancer patients.Table 2

Bottom Line: M2 tumor-associated macrophages (M2-TAMs) also play an important role in cancer progression.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus