BACKGROUNDThe interactions between cancer stem cells (CSCs) and tumor-associated macrophages (TAMs) can promote tumor progression, maintain the CSCs population, and reduce therapeutic effects. The objective of this study was to investigate the coexpression of CSCs and TAMs and its clinical significance in pancreatic ductal adenocarcinoma (PDAC).METHODSNinety-six patients with PDAC were included in this study. Tissue microarrays were constructed for immunostaining of the CSCs markers CD44 and CD133 and the TAMs marker CD204. Correlations between the expression of CSCs and TAMs markers and clinicopathologic characteristics or disease progression were analyzed.RESULTSExpression levels of CD44/CD133 and CD204 were significantly higher in tumor tissues than in normal tissues (P < .0001). The variables associated with survival were high coexpression of CD44/CD133 (P = .000), high expression of CD204 (P = .011), and tumor grade (P = .014). There was a positive correlation between CD44/CD133 and CD204 expression (r = 0.294; P = .004). Survival analysis indicated that high coexpression of CD44/CD133 and CD204 was associated significantly with shorter overall survival (P = .000) and disease-free survival (P = .003). Multivariate analysis revealed that high CD44/CD133 expression was an independent prognostic factor for disease-free survival, whereas high CD204 expression was an independent predictor for both overall and disease-free survival.CONCLUSIONSCoexpression of CD44/CD133 and CD204 is a useful survival prediction marker for patients with PDAC. Cancer 2014;120:2766–2777. © The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.The clinical significance of pancreatic cancer stem cells and tumor-associated macrophages is explored in patients with pancreatic ductal adenocarcinoma. The results clearly demonstrate that coexpression of 2 cancer stem cell markers (CD44 and CD133) and a tumor-associated macrophage marker (CD204) is a useful prognostic factor for predicting the survival of patients with pancreatic ductal adenocarcinoma after surgery.
Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was negatively correlated with total psoas area (TPA). IL-8 expression in tissue samples was also positively associated with weight loss. Furthermore, serum IL-8 level was an independent predictor of survival. In conclusion, elevated serum IL-8 level significantly correlates with CC and sarcopenia and can be used as a prognostic indicator in PC.
BackgroundOsteopontin (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.MethodsThe 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.ResultsPatients 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.ConclusionOPN 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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