title: Overexpression of Notch ligand Dll1 in B16 melanoma cells leads to reduced tumor growth due to attenuated vascularization.
abstract: Notch signaling plays an important role in vascular development and tumor angiogenesis. It has been shown that disruption of Dll4-triggered Notch signal activation effectively inhibits tumor growth, but this treatment also results in the formation of vascular neoplasms. In this study, we investigate the effects of over-expressing Notch ligand Dll1 in B16 melanoma cells on tumor cell proliferation and tumor growth in vitro and in vivo. Our results showed that over-expression of Dll1 could activate Notch signaling in tumor cells, and promote tumor cell proliferation in vitro. In contrast, growth of Dll1-over-expressing tumors in vivo was reduced, due to abnormal tumor vessel formation. Impaired tumor vasculature enhanced hypoxia and necrosis in tumor tissues, leading to retarded tumor growth. These results suggest that activation of Notch signaling may serve as an anti-angiogenesis strategy in the treatment of malignant tumors.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xian 710032, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Xing-Cheng
authors.initials: XC
authors.lastname: Zhao
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Cai
authors.forename: Ya-Ning
authors.initials: YN
authors.lastname: Wei
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D009336:Necrosis; D009389:Neovascularization, Pathologic; D051881:Receptor, Notch1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012878:Skin Neoplasms; D042461:Vascular Endothelial Growth Factor A
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D042461:Vascular Endothelial Growth Factor A