CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer

• Published in: Cell death & disease Vol. 9; no. 10; pp. 974 - 16
• Main Authors: Xu, Zhuoqing, Zhu, Congcong, Chen, Chun, Zong, Yaping, Feng, Hao, Liu, Di, Feng, Wenqing, Zhao, Jingkun, Lu, Aiguo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-09-2018; Springer Nature B.V
• Subjects: 13; 13/1; 13/109; 13/51; 38; 38/77; 38/90; 64/60; 82/80; Aged; Angiogenesis; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; CCL19 protein; CCR7 protein; Cell Biology; Cell Culture; Cell Line, Tumor; Chemokine CCL19 - metabolism; Chemokines; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood supply; ets-Domain Protein Elk-1 - antagonists & inhibitors; ets-Domain Protein Elk-1 - metabolism; Extracellular signal-regulated kinase; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunohistochemistry; Immunology; Life Sciences; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - metabolism; Middle Aged; Neovascularization, Pathologic - metabolism; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Proto-Oncogene Proteins c-met - metabolism; Receptors, CCR7 - metabolism; Transplantation, Heterologous; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-1010-2

The mechanisms underlying the role of chemokines in tumor angiogenesis is still not fully understood. In this study, we detected the influence of CCL19 on colorectal cancer (CRC) angiogenesis. The expression of CCL19 and CD31 in CRC tissues were detected by immunohistochemistry. Human CRC cell lines SW1116 and SW620 stably transfected with CCL19 lentivirus and CCL19 shRNA, and HUVEC stably transfected with CCR7 shRNA were used in our study. Our study showed that CCL19 was significantly low-expressed in CRC tissues and positively related to highly tumor microvessel density. In vitro, we observed that CCL19 high-expressed SW1116 supernatant was able to inhibit proliferation, migration, and sprouting responses of HUVEC, whereas CCL19 low-expressed SW620 supernatant can promote HUVEC angiogenesis. Additionally, we further demonstrated that these functions maybe achieved through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in a CCR7-dependent manner. Mice angiogenesis model also confirmed that elevated expression of CCL19 inhibit the angiogenesis of CRC in vivo. In summary, our results supported that CCL19 can inhibit CRC angiogenesis through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway. This may be a novel therapeutic option for anti-vascular treatment in CRC.