CCL19/CCR7 upregulates heparanase via specificity protein-1 (Sp1) to promote invasion of cell in lung cancer.

Abstract

CCL19/chemokine receptor 7 (CCR7) has been found to be associated with tumor growth, angiogenesis, invasion, and lymph node metastasis. Our previous study demonstrated that CCR7 overexpressed in non-small cell lung cancer (NSCLC) and had close relationship with tumor invasion and lymph node metastasis. However, the molecular mechanism of CCR7 promoting invasion of human NSCLC cells is still unclear. In this study, we demonstrated that human lung adenocarcinoma A549 cells treated with recombinant human CCL19 could obviously upregulate the expression of Sp1 and heparanase at both the mRNA and protein levels. After blockage of CCR7, Sp1 and heparanase expressions were inhibited. Following inhibition of Sp1, heparanase expression was downregulated. The analysis showed the promoter region of heparanase gene containing a number of potential sp1 binding sites (5'-GGGGC-3'). Chromatin immunoprecipitation analysis demonstrated that Sp1 could bind to the heparanase promoter. Cell invasion assays showed that the invasion ability of A549 cells was increased with CCL19 incubation compared to the control cells. These results suggested that CCL19/CCR7 may upregulate the expression of heparanase via Sp1 and contribute to the invasion of A549 cells.

• Authors: Qingfu Zhang, Limei Sun, Liying Yin, Jian Ming, Siyang Zhang, Wenting Luo, Xueshan Qiu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 5 Pg. 2703-8 (Oct 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23649655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL19 protein, human
• CCR7 protein, human
• Chemokine CCL19
• Receptors, CCR7
• Sp1 Transcription Factor
• heparanase
• Glucuronidase
• Metalloendopeptidases
• damage-induced neuronal endopeptidase

Topics

• Base Sequence
• Cell Line, Tumor
• Cell Movement
• Chemokine CCL19 (physiology)
• Consensus Sequence
• Enzyme Induction
• Gene Expression Regulation, Neoplastic
• Glucuronidase (genetics, metabolism)
• Humans
• Lung Neoplasms (enzymology, pathology)
• Metalloendopeptidases
• Molecular Sequence Data
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• Protein Binding
• Receptors, CCR7 (physiology)
• Sp1 Transcription Factor (metabolism)
• Up-Regulation