Abstract
Glioblastoma (GBM) is the most lethal primary nervous system cancer, but due to its rarity and complexity, its pathogenesis is poorly understood. To identify potential tumorigenic factors in GBM, we screened antibody-based cytokine arrays and found that CCL11 was upregulated. We then demonstrated in vitro that both CCL11 and its receptor, CCR3, were overexpressed and promoted the proliferation, migration and invasion of cancer cells. To examine the clinical significance of CCL11/CCR3, 458 GBM samples were divided into a training cohort with 225 cases and a test cohort containing 233 cases. In the training set, immunohistochemical analysis showed overexpression of CCL11 and CCR3 were correlated with unfavorable overall survival (OS). We further developed a prognostic classifier combining CCL11 and CCR3 expression and Karnofsky performance status (KPS) for predicting one-year survival in GBM patients. Receiver operating characteristic (ROC) analysis demonstrated that this predictor achieved 90.7% sensitivity and 73.4% specificity. These results were validated with the test sample set. Our findings suggest that CCL11-CCR3 binding is involved in the progression of GBM and may prompt a novel therapeutic approach. In addition, CCL11 and CCR3 expression, combined with KPS, may be used as an accurate predictor of one-year survival in GBM patients.
Highlights
Glioblastoma multiforme (GBM) is the most fatal primary brain tumor
Since previous studies had shown that RANTES [15] and CX3CL1 [16] expression were correlated with the development of GBM, we focused on elucidating the role of CCL11
Real-time quantitative PCR demonstrated that CCL11 was overexpressed in 8 freshly collected GBM samples compared with paired adjacent tissue from the same subject (Figure 1B, left panel)
Summary
Glioblastoma multiforme (GBM) is the most fatal primary brain tumor. Due to the poor efficacy of conventional therapeutics, the median survival period of GBM patients is only about one year [1]. CCL11, known as eotaxin-1, is an eosinophil-selective chemoattractant cytokine. It is widely expressed in human tissues including heart, colon, kidney, small intestine, lung, pancreas, liver, and ovary [3, 4]. CCL11 primarily binds to CCR3, a seven-transmembranedomain G-protein-coupled chemokine receptor [5]. This binding triggers a series of signal transduction events involving transient release of intracellular calcium, cytoskeletal rearrangements, generation of inositol triphosphate, activation of protein kinase C and prolonged receptor internalization into an endocytic compartment [5,6,7]. The association between CCL11/CCR3 and GBM has not been adequately investigated
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