Upregulation of chemokine receptor CCR10 is essential for glioma proliferation, invasion and patient survival.

Abstract

Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Tumor cell invasion share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptor CCR10 is highly expressed in human glioblastoma compared with control brain tissue. In vitro, signaling through CCL27-CCR10 mediates activation of p-Akt, and subsequently induces proliferation and invasive responses. Cell proliferation and invasion promoted by CCL27 were blocked by inhibition of p-Akt or CCR10. In vivo, down-regulation of CCR10 significantly impairs growth of glioma. Clinically, High CCR10 expression in GBM correlated with p-Akt, shorter overall survival and progression-free survival (P < 0.05). Together, these findings suggest that elevated CCR10 is a critical molecular event associated with gliomagenesis.

• Authors: Lingchao Chen, Xing Liu, Hai-Yan Zhang, Wenzong Du, Zhiyong Qin, Yu Yao, Ying Mao, Liangfu Zhou
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 16 Pg. 6576-83 (Aug 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25149529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR10 protein, human
• Receptors, CCR10
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Proliferation (physiology)
• Glioblastoma (genetics, metabolism, pathology)
• Heterografts
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, CCR10 (biosynthesis, genetics, metabolism)
• Survival Analysis
• Transfection
• Up-Regulation