Skip to main content
Top
Published in: Clinical & Experimental Metastasis 5/2013

01-06-2013 | Research Paper

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

Authors: Li Wang, Shaoxian Tang, Yingjian Wang, Siguang Xu, Jerry Yu, Xiuling Zhi, Zhouluo Ou, Jiayin Yang, Ping Zhou, Zhimin Shao

Published in: Clinical & Experimental Metastasis | Issue 5/2013

Login to get access

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.
Literature
1.
2.
go back to reference Zimmermann H (1992) 5′-Nucleotidase: molecular structure and functional aspects. Biochem J 285(Pt 2):345–365PubMed Zimmermann H (1992) 5′-Nucleotidase: molecular structure and functional aspects. Biochem J 285(Pt 2):345–365PubMed
3.
go back to reference Burger RM, Lowenstein JM (1975) 5′-Nucleotidase from smooch muscle of small intestine and from brain. Inhib nudeotides Biochem 14(11):2362–2366CrossRef Burger RM, Lowenstein JM (1975) 5′-Nucleotidase from smooch muscle of small intestine and from brain. Inhib nudeotides Biochem 14(11):2362–2366CrossRef
4.
go back to reference Colgan SP, Eltzschig HK, Eckle T et al (2006) Physiological roles for ecto-50-nucleotidase (CD73). Purinergic Signal 2(2):351–360PubMedCrossRef Colgan SP, Eltzschig HK, Eckle T et al (2006) Physiological roles for ecto-50-nucleotidase (CD73). Purinergic Signal 2(2):351–360PubMedCrossRef
5.
go back to reference Obata T (2002) Adenosine production and its interaction with protection of ischemic and reperfusion injury of the myocardium. Life Sci 71(18):2083–2103PubMedCrossRef Obata T (2002) Adenosine production and its interaction with protection of ischemic and reperfusion injury of the myocardium. Life Sci 71(18):2083–2103PubMedCrossRef
6.
go back to reference Zernecke A, Bidzhekov K, Ozüyaman B et al (2006) CD73/Ecto-5′-nucleotidase protects against vascular inflammation and neointima formation. Circ Res 113(17):2120–2127CrossRef Zernecke A, Bidzhekov K, Ozüyaman B et al (2006) CD73/Ecto-5′-nucleotidase protects against vascular inflammation and neointima formation. Circ Res 113(17):2120–2127CrossRef
7.
go back to reference Ramkumar V, Pierson G, Stiles G (1988) Adenosine receptors: clinical implications and biochemical mechanisms. Prog Drug Res 32:195–247PubMed Ramkumar V, Pierson G, Stiles G (1988) Adenosine receptors: clinical implications and biochemical mechanisms. Prog Drug Res 32:195–247PubMed
8.
go back to reference Regina R, Thompson LF (1997) T cell signalling through CD73. Cell Signal 9(2):131–139CrossRef Regina R, Thompson LF (1997) T cell signalling through CD73. Cell Signal 9(2):131–139CrossRef
9.
go back to reference Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109PubMedCrossRef Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109PubMedCrossRef
10.
go back to reference Airas L, Hellman J, Salmi M et al (1995) CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte-vascular adhesion protein 2 identifies it as CD73. J Exp Med 182(5):1603–1608PubMedCrossRef Airas L, Hellman J, Salmi M et al (1995) CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte-vascular adhesion protein 2 identifies it as CD73. J Exp Med 182(5):1603–1608PubMedCrossRef
11.
go back to reference Airas L, Jalkanen S (1996) CD73 mediates adhesion of B cells to follicular dendritic cells. Blood 88(5):1755–1764PubMed Airas L, Jalkanen S (1996) CD73 mediates adhesion of B cells to follicular dendritic cells. Blood 88(5):1755–1764PubMed
12.
go back to reference Airas L, Niemelä J, Salmi M et al (1997) Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells. J Cell Biol 136(2):421–431PubMedCrossRef Airas L, Niemelä J, Salmi M et al (1997) Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells. J Cell Biol 136(2):421–431PubMedCrossRef
13.
go back to reference Wang L, Zhou X, Zhou P et al (2008) Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells. J Cancer Res Clin Oncol 134(3):365–372PubMedCrossRef Wang L, Zhou X, Zhou P et al (2008) Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells. J Cancer Res Clin Oncol 134(3):365–372PubMedCrossRef
14.
go back to reference Sadej R, Spychala J, Skladanowski AC (2006) Expression of ecto-5 ‘-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma. Melanoma Res 16(3):213–222PubMedCrossRef Sadej R, Spychala J, Skladanowski AC (2006) Expression of ecto-5 ‘-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma. Melanoma Res 16(3):213–222PubMedCrossRef
15.
go back to reference Kruger KH, Thompson LF, Kaufmann M et al (1991) Expression of ecto-5′-nucleotidase (CD73) in normal mammary gland and in breast carcinoma. Br J Cancer 63(1):114–118PubMedCrossRef Kruger KH, Thompson LF, Kaufmann M et al (1991) Expression of ecto-5′-nucleotidase (CD73) in normal mammary gland and in breast carcinoma. Br J Cancer 63(1):114–118PubMedCrossRef
16.
go back to reference Kondo T, Nakazawa T, Murata SI et al (2006) Expression of CD73 and its ecto-5′-nucleotidase activity are elevated in papillary thyroid carcinomas. Histopathology 48(5):612–614PubMedCrossRef Kondo T, Nakazawa T, Murata SI et al (2006) Expression of CD73 and its ecto-5′-nucleotidase activity are elevated in papillary thyroid carcinomas. Histopathology 48(5):612–614PubMedCrossRef
17.
go back to reference Durak I, Cetin R, Canbolat O et al (1994) Adenosine deaminase, 5′-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer. Cancer Lett 84(2):199–202PubMedCrossRef Durak I, Cetin R, Canbolat O et al (1994) Adenosine deaminase, 5′-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer. Cancer Lett 84(2):199–202PubMedCrossRef
18.
go back to reference Flocke K, Mannherz HG (1991) Isolation and characterization of 5′-nucleotidase of a human pancreatic tumor cell line. Biochim Biophys Acta 1076(2):273–281PubMedCrossRef Flocke K, Mannherz HG (1991) Isolation and characterization of 5′-nucleotidase of a human pancreatic tumor cell line. Biochim Biophys Acta 1076(2):273–281PubMedCrossRef
19.
go back to reference Fenoglio C, Necchi D, Civallero M et al (1997) Cytochemical demonstration of nitric oxide synthase and 5′ nucleotidase in human glioblastoma. Anticancer Res 17(4A):2507–2511PubMed Fenoglio C, Necchi D, Civallero M et al (1997) Cytochemical demonstration of nitric oxide synthase and 5′ nucleotidase in human glioblastoma. Anticancer Res 17(4A):2507–2511PubMed
20.
go back to reference Minamino T, Kitakaze M, Komamura K et al (1995) Activation of protein kinase C increases adenosine production in the hypoxic canine coronary artery through the extracellular pathway. Arterioscler Thromb Vasc Biol 15(12):2298–2304PubMedCrossRef Minamino T, Kitakaze M, Komamura K et al (1995) Activation of protein kinase C increases adenosine production in the hypoxic canine coronary artery through the extracellular pathway. Arterioscler Thromb Vasc Biol 15(12):2298–2304PubMedCrossRef
21.
go back to reference Le Hir M, Kaissling B (1993) Distribution and regulation of renal ecto-5′-nucleotidase: implications for physiological functions of adenosine. Am J Physiol 264(3 Pt 2):F377–F387PubMed Le Hir M, Kaissling B (1993) Distribution and regulation of renal ecto-5′-nucleotidase: implications for physiological functions of adenosine. Am J Physiol 264(3 Pt 2):F377–F387PubMed
22.
go back to reference Braun N, Lenz C, Gillardon F et al (1997) Focal cerebral ischemia enhances glial expression of ecto-5′-nucleotidase. Brain Res 766(1–2):213–226PubMedCrossRef Braun N, Lenz C, Gillardon F et al (1997) Focal cerebral ischemia enhances glial expression of ecto-5′-nucleotidase. Brain Res 766(1–2):213–226PubMedCrossRef
23.
go back to reference Thompson LF, Eltzschig HK, Ibla JC et al (2004) Crucial role for ecto-5-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200(11):1395–1405PubMedCrossRef Thompson LF, Eltzschig HK, Ibla JC et al (2004) Crucial role for ecto-5-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200(11):1395–1405PubMedCrossRef
24.
go back to reference Sommerschild HT, Kirkeboen KA (2000) Adenosine and cardioprotection during ischaemia and reperfusion: an overview. Acta Anaesthesiol Scand 44(9):1038–1055PubMedCrossRef Sommerschild HT, Kirkeboen KA (2000) Adenosine and cardioprotection during ischaemia and reperfusion: an overview. Acta Anaesthesiol Scand 44(9):1038–1055PubMedCrossRef
25.
go back to reference Zhou P, Zhi X, Zhou T et al (2007) Overexpression of Ecto-5′-nucleotidase (CD73) promotes T-47D human breast cancer cells invasion and adhesion to extracellular matrix. Cancer Biol Ther 6(3):426–431PubMedCrossRef Zhou P, Zhi X, Zhou T et al (2007) Overexpression of Ecto-5′-nucleotidase (CD73) promotes T-47D human breast cancer cells invasion and adhesion to extracellular matrix. Cancer Biol Ther 6(3):426–431PubMedCrossRef
26.
go back to reference Zhi X, Chen S, Zhou P et al (2007) RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion. Clin Exp Metastasis 24(6):439–448PubMedCrossRef Zhi X, Chen S, Zhou P et al (2007) RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion. Clin Exp Metastasis 24(6):439–448PubMedCrossRef
28.
go back to reference Macchiarini P, Fontanini G, Hardin MJ et al (1992) Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 340(8812):145–146PubMedCrossRef Macchiarini P, Fontanini G, Hardin MJ et al (1992) Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 340(8812):145–146PubMedCrossRef
29.
go back to reference Weidner N (1995) Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 147(1):9–19PubMed Weidner N (1995) Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 147(1):9–19PubMed
30.
go back to reference Zhou X, Zhi X, Zhou P et al (2007) Effects of ecto-5′-nucleotidase on human breast cancer cell growth in vitro and in vivo. Oncol Rep 17(6):1341–1346PubMed Zhou X, Zhi X, Zhou P et al (2007) Effects of ecto-5′-nucleotidase on human breast cancer cell growth in vitro and in vivo. Oncol Rep 17(6):1341–1346PubMed
31.
go back to reference Turnay J, Olmo N, Risse G et al (1989) 5-Nucleotidase activity in cultured cell lines. Effect of different assay conditions and correlation with cell proliferation. In Vitro Cell Dev Biol 25(11):1055–1061PubMedCrossRef Turnay J, Olmo N, Risse G et al (1989) 5-Nucleotidase activity in cultured cell lines. Effect of different assay conditions and correlation with cell proliferation. In Vitro Cell Dev Biol 25(11):1055–1061PubMedCrossRef
32.
go back to reference Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14(1):53–65PubMedCrossRef Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14(1):53–65PubMedCrossRef
33.
go back to reference Stochaj U, Mannherz HG (1992) Chicken gizzard 5′-nucleotidase functions as a binding protein for the laminin/nidogen complex. Eur J Cell Biol 59(2):364–372PubMed Stochaj U, Mannherz HG (1992) Chicken gizzard 5′-nucleotidase functions as a binding protein for the laminin/nidogen complex. Eur J Cell Biol 59(2):364–372PubMed
35.
go back to reference Stefanová I, Horejsí V, Ansotegui IJ et al (1991) GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 254(5034):1016–1019PubMedCrossRef Stefanová I, Horejsí V, Ansotegui IJ et al (1991) GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 254(5034):1016–1019PubMedCrossRef
Metadata
Title
Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis
Authors
Li Wang
Shaoxian Tang
Yingjian Wang
Siguang Xu
Jerry Yu
Xiuling Zhi
Zhouluo Ou
Jiayin Yang
Ping Zhou
Zhimin Shao
Publication date
01-06-2013
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 5/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-013-9571-z

Other articles of this Issue 5/2013

Clinical & Experimental Metastasis 5/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine