RESUMO
The scavenger receptor stabilin-1 has been reported to be expressed by tumor-associated macrophages (TAMs) and to facilitate tumor growth and metastasis in mouse models of breast carcinoma and melanoma. However, to the best of our knowledge, its expression and association with prognosis in human gastric cancer has not been evaluated. The present study investigated the expression of stabilin-1 and its association with clinicopathological parameters in patients with gastric cancer. The expression of stabilin-1 was evaluated by immunohistochemical staining of gastric cancer tissue samples of 371 Chinese patients with primary gastric adenocarcinoma. Confocal laser scanning microscopy was used to determine the cellular source of stabilin-1 in the gastric cancer tissues using anti-CD68, anti-CD163, anti-stabilin-1 and anti-secreted protein acidic and rich in cysteine antibodies. A higher number of stabilin-1-positive cells were observed in the cancer tissues of primary gastric adenocarcinoma compared with adjacent non-cancerous tissues of primary gastric adenocarcinoma (P<0.001); the majority of stabilin-1-positve cells were CD68+/CD163+ macrophages. Poorly-differentiated gastric cancer tissue had fewer stabilin-1-positive cells compared with medium- and well-differentiated gastric cancer (P=0.030). A higher number of stabilin-1-positive cells were found in the early Tumor-Node-Metastasis (TNM) stage (TNM I stage) of primary gastric adenocarcinoma (P=0.038) compared with TNM stage IV. For patients with TNM stage I disease, a higher number of stabilin-1-positive TAMs was associated with shorter cumulative survival (P<0.05). Overall, stabilin-1 was found to be expressed by CD68+ TAMs in human gastric cancer. The high expression of stabilin-1 in TNM stage I disease was associated with poor patient survival, indicating the clinical significance of stabilin-1 in gastric cancer.
RESUMO
BACKGROUND: Mannose receptor (MR) is an immune adhesion molecule and is mainly expressed in macrophages and nonmature dendritic cells. The ligand mannose, one of the natural ligands of MR, is a monosaccharide, which is localized in the envelope or cytoplasm of macrophages. The aim of this study was to investigate expression of MR and its ligand mannose in tumor tissues of primary advanced gastric cancer and to evaluate the predictive and prognostic value of the positive cells in gastric cancer patients. METHODS: Histochemical staining for Narcissus pseudonarcissus lectin (NPL) and immunohistochemical envision two-step assay for MR were used to detect expression of NPL and MR in primary advanced gastric adenocarcinoma tissues. Adjacent non-cancerous gastric tissues of the patients were used as controls. Relationship of NPL and MR expression in the tumor tissues with clinicopathological features and survival time of the gastric cancer patients were analyzed. RESULTS: Numbers of NPL+ and MR+ macrophages in stromal tissues of gastric cancer were significantly higher than those in the adjacent non-cancerous gastric tissues (P=0.006; P<0.001). NPL expression in the primary tumor tissues was significantly more dominant than that in the adjacent non-cancerous gastric tissues (P=0.003). Expression of both the molecules in macrophages in tumor tissues was negatively correlated (r=-0.363, P=0.009). TNM stage of the patients was closely correlated to number of MR+ macrophages and NPL expression in the stromal tissues of gastric cancer (P=0.009 and P=0.020). Kaplan-Meier survival model data showed that the patients with low counting of NPL+ macrophages and high counting of MR+ macrophages significantly led to worse disease progression and poorer prognosis (P=0.008). Cox regression analysis further demonstrated that high expression of MR+ macrophages was an independent predictor of poor prognosis in patients with gastric cancer (P=0.033). CONCLUSIONS: Occurrence of mannose and MR in tumor tissues of gastric cancer might be prognostic factors for estimating risk of gastric cancer patients.
RESUMO
BACKGROUND: We aimed to investigate the cellular source of secreted protein acidic and rich in cysteine (SPARC) in gastric cancer tissues and the relationship between SPARC expression and its prognostic significance. METHODS: The expression of SPARC in 365 primary advanced gastric adenocarcinomas and 39 non-cancerous tissues was evaluated by immunohistochemical staining. Double-immunofluorescence staining was used to reveal the cellular source of SPARC in tumor tissues. Western blotting and immunofluorescence staining were applied for verifying the endogenous expression of SPARC in human cell lines of gastric cancer and fibroblast. RESULTS: Higher positivity of SPARC was observed in gastric cancer tissues than non-cancerous gastric tissues (P=0.000). The positivity of SPARC was related to age (P=0.032), tumor location (P=0.018), depth of tumor invasion (P=0.011), nodal metastasis (P=0.023), TNM stage (P=0.034), the differentiation degree (P=0.006) and pathological type (P=0.002) of gastric cancer. SPARC in gastric cancer tissues was mainly expressed by cancer-associated fibroblasts. SPARC also appeared in neovascular endothelial cells and a few tumor-associated macrophages. The endogenous expression of SPARC in fibroblasts was suppressed by mucus-producing gastric adenocarcinoma cells(MKN-45). Increased SPARC expression in gastric cancer tissue was suggestive of a shorter cumulative survival in the patients with gastric adenocarcinoma, though this difference was not statistically significant(P>0.05). CONCLUSION: SPARC in human gastric cancer tissue was derived from the stromal cells and was mainly produced by cancer-associated fibroblasts. Production of SPARC in fibroblasts was reduced by the mucus-producing gastric adenocarcinoma cells.
