Silencing of CCR7 inhibits the growth, invasion and migration of prostate cancer cells induced by VEGFC.
Early in prostate cancer development, tumor cells express vascular endothelial growth factor C (VEGF-C), a secreted molecule that is important in angiogenesis progression. CC-chemokine receptor 7 (CCR7), another protein involved in angiogenesis, is strongly expressed in most human cancers, where it activated promotes tumor growth as well as favoring tumor cell invasion and migration. The present study aimed to investigate the effect of down-regulating CCR7 expression on the growth of human prostate cancer cells stimulated by VEGFC. The CCR7-specific small interfering RNA (siRNA) plasmid vector was constructed and then transfected into prostate cancer cells. The expression of CCR7 mRNA and protein was detected by quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation, apoptosis, cell cycle distribution and cell migration were assessed following knockdown of CCR7 by RNA interference (RNAi). Western blot analysis was used to identify differentially expressed angiogenesis- and cell cycle-associated proteins in cells with silenced CCR7. The expression levels of CCR7 in prostate cancer cells transfected with siRNA were decreased, leading to a significant inhibition of prostate cancer cell proliferation, migration and invasion induced by VEGFC. Western blot analysis revealed that silencing of CCR7 may inhibit vascular endothelial growth factor, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. In conclusion, the present study demonstrated that RNAi can effectively silence CCR7 gene expression and inhibit the growth of prostate cancer cells, which indicates that there is a potential of targeting CCR7 as a novel gene therapy approach for the treatment of prostate cancer.
['Chi|Bao-Jin|BJ|', 'Du|Cong-Lin|CL|', 'Fu|Yun-Feng|YF|', 'Zhang|Ya-Nan|YN|', 'Wang|Ru Wen|RW|']
D000818:Animals D015153:Blotting, Western D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D015536:Down-Regulation D005260:Female D055785:Gene Knockdown Techniques D064593:Heterografts D006801:Humans D008297:Male D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D009361:Neoplasm Invasiveness D009389:Neovascularization, Pathologic D016133:Polymerase Chain Reaction D011471:Prostatic Neoplasms D034741:RNA, Small Interfering D054400:Receptors, CCR7 D014162:Transfection D042582:Vascular Endothelial Growth Factor C
CCR7 Prostate cancer VEGFC