Overexpression of Notch ligand Dll1 in B16 melanoma cells leads to reduced tumor growth due to attenuated vascularization.
Overexpression of Notch ligand Dll1 in B16 melanoma cells leads to reduced tumor growth due to attenuated vascularization.
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DOI：
10.1016/j.canlet.2011.06.008
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发表时间：
2011-10
期刊：
影响因子：
9.7
通讯作者：
Jian‐ping Zhang;Hongyan Qin;L. Wang;Liang Liang-Liang;Xingcheng Zhao;W. Cai;Ya-Ning Wei;Chun-mei Wang;Hua Han
中科院分区：
文献类型：
--
作者：
Jian‐ping Zhang;Hongyan Qin;L. Wang;Liang Liang-Liang;Xingcheng Zhao;W. Cai;Ya-Ning Wei;Chun-mei Wang;Hua Han
Notch信号在血管发育和肿瘤血管生成中起重要作用。研究表明，阻断DLL4触发的Notch信号激活有效地抑制了肿瘤的生长，但这种治疗也会导致血管肿瘤的形成。在本研究中，我们研究了在B16黑色素瘤细胞中过表达Notch配体DLL1在体内外对肿瘤细胞增殖和肿瘤生长的影响。我们的结果表明，过表达Dll1可以激活肿瘤细胞中的Notch信号，并在体外促进肿瘤细胞的增殖。相比之下，体内过表达DLL1的肿瘤由于异常的肿瘤血管形成而生长减少。肿瘤血管受损增加了肿瘤组织中的缺氧和坏死，导致肿瘤生长受阻。这些结果表明，激活Notch信号通路可能在恶性肿瘤的治疗中作为一种抗血管生成的策略。
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.