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Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis

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Abstract

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.

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Abbreviations

APCP:

α,β-Methylene adenosine-5′-diphosphate

ATCC:

American type culture collection

BCA:

Bicinchoninic acid

CD73:

Ecto-5′-nucleotidase

DiI-Ac-LDL:

Low-density lipoprotein from human plasma, acetylated, DiI complex

FBS:

Fetal bovine serum

HUVECs:

Human umbilical vein endothelial cells

NBS:

Newborn bovine serum

Neo gene:

Antineomycin gene

OD:

Optical density

PAGE:

Polyacrylamide gel electrophoresis

PBS:

Phosphate-buffered saline

PVDF:

Polyvinylidene fluoride

PMECs:

Pulmonary microvascular endothelial cells

SDS:

Sodium dodecyl sulfate

VCAM-1:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial growth factor

5′-AMP:

Adenosine 5′-monophosphate

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Acknowledgments

We thank Professor Linda Thompson from Okalahoma University in USA for her generous support with wild type (CD73+/+) and CD73 gene knockout (CD73−/−) C57BL/6 mice and CD73+/+and CD73−/− BALB/c mice. This work was supported by National Natural Science Foundation of China (30971163) (81172507) and (81001170).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, No. 138 Yixueyuan Road, Shanghai, 200032, China

    Li Wang, Shaoxian Tang, Jerry Yu, Xiuling Zhi, Jiayin Yang & Ping Zhou

  2. Department of Medicine, University of Louisville, Louisville, KY, 40292, USA

    Jerry Yu

  3. Department of Breast Surgery, Cancer Hospital, Fudan University, Shanghai, 200032, China

    Siguang Xu, Zhouluo Ou & Zhimin Shao

  4. Department of Gynaecology and Obsterics, China–Japan Union Hospital of Jilin University, Changchun, China

    Yingjian Wang

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  1. Li Wang
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  2. Shaoxian Tang
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  4. Siguang Xu
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Corresponding authors

Correspondence to Ping Zhou or Zhimin Shao.

Additional information

Li Wang and Shaoxian Tang contributed equally to this study.

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Wang, L., Tang, S., Wang, Y. et al. Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis. Clin Exp Metastasis 30, 671–680 (2013). https://doi.org/10.1007/s10585-013-9571-z

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  • DOI: https://doi.org/10.1007/s10585-013-9571-z

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