Abstract
AimsAltered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC.Methods and ResultsQuantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features.ConclusionsLoss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.
Highlights
Like normal tissues, tumors are composed of two discrete but interactive compartments, the parenchyma and the stroma
intestinal metaplasia (IM), gastritis with IM and gastric cancer (GC) were assessed by quantum dots (QDs)-IHC using the Cav-1 polyclonal antibody
Colocalization of Cav-1 and a-SMA proteins was detected by QDs-based double immunofluorescent labeling in the GC, and analyzed by multispectral imaging systems, to precisely identify Cav-1 expression in cancer associated fibroblasts (CAFs) (Fig. 3)
Summary
Tumors are composed of two discrete but interactive compartments, the parenchyma and the stroma. The tumor cells themselves are parenchyma, whereas the stroma includes a mixture of extracellular matrix (ECM) elements and non-malignant cells, such as cancer associated fibroblasts (CAFs), vascular endothelial cells and immune and inflammatory cells [1,2,3]. Tumor cells can trigger the deposition of a reactive stroma containing activated CAFs, immune and inflammatory cells, ECM elements that may favor invasion and metastasis of cancers [2,3]. It is increasingly clear that Cav-1 is implicated in regulating multiple cancerassociated processes, ranging from cellular transformation, tumor growth, invasion and metastasis, to multidrug resistance and angiogenesis [14]. Especially the CAFs, low expression of Cav-1 protein predicts adverse outcome in breast and prostate cancer [4,5,6,8,12,15]. We hypothesis that roles of Cav-1 in epithelial and stroma may be different, roles of epithelial Cav-1 is uncertain but low expression of Cav-1 in CAFs may promotes GC progression and correlates with adverse outcome of GC patients
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