title: 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: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, People's Republic of China, qingfu1981@126.com.
authors: Qingfu
authors: Q
authors: Zhang
authors: Limei
authors: L
authors: Sun
authors: Liying
authors: L
authors: Yin
authors: Jian
authors: J
authors: Ming
authors: Siyang
authors: S
authors: Zhang
authors: Wenting
authors: W
authors: Luo
authors: Xueshan
authors: X
authors: Qiu
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000502:physiology*; D016384:Consensus Sequence; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054400:Receptors, CCR7 / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D054415:Chemokine CCL19; D005966:Glucuronidase; D008666:Metalloendopeptidases; D054400:Receptors, CCR7; D016329:Sp1 Transcription Factor; D000099175:Heparanase; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C407822:damage-induced neuronal endopeptidase
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