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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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The overall survival of gastric cancer patients with variable OPN and CD204 expression was analyzed. Either high OPN expression (>50% positive staining, p = 0.0055) or high CD204 expression (>50% positive staining, p = 0.0498) in gastric cancer was correlated with lower overall survival. However, the most significant reduction in overall survival occurred for patients with high co-expression of OPN and CD204 (p = 0.0131). The 5-year survival rate in high OPN expression patients was 48.61%, in low OPN expression was 70.42%, in low CD204 expression was 66.80%, in high CD204 expression was 52.14%, in high co-expression of OPN and CD204 was 48.9%, and in low co-expression of OPN and CD204 was 82.10%.
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Fig3: The overall survival of gastric cancer patients with variable OPN and CD204 expression was analyzed. Either high OPN expression (>50% positive staining, p = 0.0055) or high CD204 expression (>50% positive staining, p = 0.0498) in gastric cancer was correlated with lower overall survival. However, the most significant reduction in overall survival occurred for patients with high co-expression of OPN and CD204 (p = 0.0131). The 5-year survival rate in high OPN expression patients was 48.61%, in low OPN expression was 70.42%, in low CD204 expression was 66.80%, in high CD204 expression was 52.14%, in high co-expression of OPN and CD204 was 48.9%, and in low co-expression of OPN and CD204 was 82.10%.

Mentions: Kaplan-Meier survival analysis was used to determine the overall survival of patients with gastric cancer (Figure 3). Patients with high expression of OPN demonstrated significantly worse overall survival than those with low expression of OPN (p = 0.0055) and the hazard ratio is 2.039 (95% CI of ratio is 1.220 to 3.406). The 5-year survival rate of gastric cancer patients with high expression OPN was 48.61%, whereas for patients with low expression OPN the 5-year survival rate was 70.42%. In M2-TAMs analysis, we found that patients with high expression of CD204 exhibited lower overall survival (p = 0.0498), hazard ratio is 1.653 (95% CI of ratio is 0.995 to 2.745) and a lower 5-year survival rate (52.14%), compared with low CD204 expressing patients. Furthermore, the 5-year survival rate of patients with high co-expression of OPN and CD204 was 48.90%, whereas that of patients with low co-expression of OPN and CD204 was 82.10%. These results suggest that high co-expression of OPN and CD204 was a marker of poor prognosis in gastric cancer.Figure 3


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)

The overall survival of gastric cancer patients with variable OPN and CD204 expression was analyzed. Either high OPN expression (>50% positive staining, p = 0.0055) or high CD204 expression (>50% positive staining, p = 0.0498) in gastric cancer was correlated with lower overall survival. However, the most significant reduction in overall survival occurred for patients with high co-expression of OPN and CD204 (p = 0.0131). The 5-year survival rate in high OPN expression patients was 48.61%, in low OPN expression was 70.42%, in low CD204 expression was 66.80%, in high CD204 expression was 52.14%, in high co-expression of OPN and CD204 was 48.9%, and in low co-expression of OPN and CD204 was 82.10%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: The overall survival of gastric cancer patients with variable OPN and CD204 expression was analyzed. Either high OPN expression (>50% positive staining, p = 0.0055) or high CD204 expression (>50% positive staining, p = 0.0498) in gastric cancer was correlated with lower overall survival. However, the most significant reduction in overall survival occurred for patients with high co-expression of OPN and CD204 (p = 0.0131). The 5-year survival rate in high OPN expression patients was 48.61%, in low OPN expression was 70.42%, in low CD204 expression was 66.80%, in high CD204 expression was 52.14%, in high co-expression of OPN and CD204 was 48.9%, and in low co-expression of OPN and CD204 was 82.10%.
Mentions: Kaplan-Meier survival analysis was used to determine the overall survival of patients with gastric cancer (Figure 3). Patients with high expression of OPN demonstrated significantly worse overall survival than those with low expression of OPN (p = 0.0055) and the hazard ratio is 2.039 (95% CI of ratio is 1.220 to 3.406). The 5-year survival rate of gastric cancer patients with high expression OPN was 48.61%, whereas for patients with low expression OPN the 5-year survival rate was 70.42%. In M2-TAMs analysis, we found that patients with high expression of CD204 exhibited lower overall survival (p = 0.0498), hazard ratio is 1.653 (95% CI of ratio is 0.995 to 2.745) and a lower 5-year survival rate (52.14%), compared with low CD204 expressing patients. Furthermore, the 5-year survival rate of patients with high co-expression of OPN and CD204 was 48.90%, whereas that of patients with low co-expression of OPN and CD204 was 82.10%. These results suggest that high co-expression of OPN and CD204 was a marker of poor prognosis in gastric cancer.Figure 3

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