title: CCL21/CCR7 up-regulate vascular endothelial growth factor-D expression via ERK pathway in human non-small cell lung cancer cells.
abstract: Lymphangiogenesis has received considerable attention and become a new research hotspot of tumor metastasis. Recently, C-C chemokine receptor 7 (CCR7) is known to promote metastasis of non-small cell lung cancer (NSCLC) cells into lymph nodes. In this study, we investigated the relationship between CCL21/CCR7 and the lymphangiogenic factor vascular endothelial growth factor (VEGF)-D in human lung cancer cells and its impact on patients' prognosis. We found that CCL21/CCR7 increase the expression of VEGF-D in NSCLC Cell Lines through induced ERK1/2 and Akt phosphorylation. In addition, our study found that the expression levels of CCR7 and CCL21 were correlated with VEGF-D, lymphatic vessels density (LVD), clinical stages, lymph node metastasis, and patient Survival in 90 human non-small cell lung cancer (NSCLC) specimens. Taken together, our results provide evidence that CCL21/CCR7 induce VEGF-D up-regulation and promote lymphangiogenesis via ERK/Akt pathway in lung cancer.
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang 110122, PR China.
authors.forename: Limei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang 110122, PR China.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang 110122, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang 110122, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang 110122, PR China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*
chemical_list: C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D054400:Receptors, CCR7; C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CCR7; NSCLC; VEGF-D; lymphangiogenesis