Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, No. 138 Yixueyuan Road, Shanghai, 200032, China.
Clin Exp Metastasis. 2013 Jun;30(5):671-80. doi: 10.1007/s10585-013-9571-z. Epub 2013 Mar 19.
Angiogenesis is essential for tumor growth, progression and metastasis. Studies indicate that expression and activity of ecto-5'-nucleotidase (CD73) are elevated in metastatic carcinomas. Our previous studies found that angiogenesis of tumor xenografts was decreased when the activity of CD73 in cancer cells was inhibited, implying that this enzyme is involved in tumor angiogenesis. To elucidate the mechanism, we investigated CD73 influence on tumor angiogenesis in both in vitro assays and in tumor bearing mice. We found that capillary-like structures were formed more in CD73(+/+) pulmonary microvascular endothelial cells (PMECs) than CD73(-/-) PMECs, and this was more pronounced when the cells were cultured in cancer-conditioned medium. Meanwhile, CD73 decreased endothelial cells adhesion to collagen IV and promoted migration. Additionally, the extent of tumor angiogenesis and the size of tumors were greater in CD73(+/+) mice than in CD73(-/-) mice. Thus, we concluded that CD73 can promote endothelial cells forming new vessels in cancer condition, facilitating tumor growth and hematogenous metastasis.
血管生成对于肿瘤的生长、进展和转移至关重要。研究表明,ecto-5'-核苷酸酶(CD73)的表达和活性在转移性癌中升高。我们之前的研究发现,当癌细胞中 CD73 的活性受到抑制时,肿瘤异种移植物的血管生成减少,这表明该酶参与了肿瘤血管生成。为了阐明机制,我们在体外实验和荷瘤小鼠中研究了 CD73 对肿瘤血管生成的影响。我们发现 CD73(+/+)肺微血管内皮细胞 (PMECs) 比 CD73(-/-) PMECs 形成更多的毛细血管样结构,当细胞在癌条件培养基中培养时,这种情况更为明显。同时,CD73 降低了内皮细胞与胶原 IV 的黏附,并促进了迁移。此外,CD73(+/+)小鼠的肿瘤血管生成程度和肿瘤大小均大于 CD73(-/-)小鼠。因此,我们得出结论,CD73 可以促进内皮细胞在癌症条件下形成新的血管,促进肿瘤生长和血行转移。