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

• DOI: 10.1038/s41419-018-1010-2
• Publication Date: 2018-09-22T14:45:32Z
• Authors: Zhuoqing Xu; Congcong Zhu; Chun Chen; Yaping Zong; Hao Feng; Di Liu; Wenqing Feng; Jingkun Zhao; Aiguo Lu
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Receptors, CCR7; Neovascularization, Pathologic; MAP Kinase Signaling System; Transplantation, Heterologous; Mice, Nude; Middle Aged; Proto-Oncogene Proteins c-met; Hypoxia-Inducible Factor 1, alpha Subunit; Article; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Human Umbilical Vein Endothelial Cells; Animals; Chemokine CCL19; Humans; Female; Colorectal Neoplasms; Aged

AbstractThe 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.