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Clinical & Experimental Metastasis

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01.10.2007 | Research Paper

RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion

verfasst von: Xiuling Zhi, Sifeng Chen, Ping Zhou, Zhimin Shao, Li Wang, Zhouluo Ou, Lianhua Yin

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 6/2007

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Abstract

Metastasis is a leading cause of mortality and morbidity in breast cancer. Recently, dramatic overexpression of ecto-5′-nucleotidase (CD73), a glycosylphosphatidylinositol-anchored cell surface protein has been found in estrogen receptor-negative [ER (−)] breast cancer cell lines and in clinical samples. In this study, CD73 small interfering RNA (siRNA) plasmid was constructed and stably transfected into breast cancer cell MB-MDA-231 to determine the role of CD73 in breast cancer metastasis and the possible mechanism. Our study demonstrates that CD73 siRNA effectively inhibits CD73 gene expression at mRNA and protein level in MB-MDA-231 cells, leading to in vivo and in vitro growth suppression, prevention of adhesion to extracellular matrix (ECM), and inhibition of invasion and migration. These properties correlate with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity as well as reduction of epidermal growth factor receptor (EGFR) expression. Demonstration of the role of CD73 in breast cancer may lead to new targeted therapies for breast cancer.

Zimmermann H (1996) Biochemistry, localization and functional roles of ecto-nucleotidases in the nervous system. Prog Neurobiol 49(6):589–618PubMedCrossRef

Resta R, Thompson LF (1997) T cell signalling through CD73. Cell Signal 9(2):131–139PubMedCrossRef

Zernecke A, Bidzhekov K, Ozuyaman B et al (2006) CD73/ecto-5′-nucleotidase protects against vascular inflammation and neointima formation. Circulation 113(17):2120–2127PubMedCrossRef

Spychala J, Lazarowski E, Ostapkowicz A et al (2004) Role of estrogen receptor in the regulation of ecto-5′-nucleotidase and adenosine in breast cancer. Clin Cancer Res 10(2):708–717PubMedCrossRef

Mujoomdar M, Bennett A, Hoskin D et al (2004) Adenosine stimulation of proliferation of breast carcinoma cell lines: evaluation of the [3H]thymidine assay system and modulatory effects of the cellular microenvironment in vitro. J Cell Physiol 201(3):429–438PubMedCrossRef

Mirza A, Basso A, Black S et al (2005) RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis. Cancer Biol Ther 4(12):1355–1360PubMedCrossRef

Spychala J (2000) Tumor-promoting functions of adenosine. Pharmacol Ther 87(2–3):161–173PubMedCrossRef

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

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

10.

Ludwig HC, Rausch S, Schallock K et al (1999) Expression of CD 73 (ecto-5′-nucleotidase) in 165 glioblastomas by immunohistochemistry and electronmicroscopic histochemistry. Anticancer Res 19(3A):1747–1752PubMed

11.

Caceres M, Guerrero J, Martinez J (2005) Overexpression of RhoA-GTP induces activation of the epidermal growth factor receptor, dephosphorylation of focal adhesion kinase and increased motility in breast cancer cells. Exp Cell Res 309(1):229–238PubMedCrossRef

12.

Ostapkowicz A, Inai K, Smith L et al (2006) Lipid rafts remodeling in estrogen receptor-negative breast cancer is reversed by histone deacetylase inhibitor. Mol Cancer Ther 5(2):238–245PubMedCrossRef

13.

Lee H, Lin EC, Liu L et al (2003) Gene expression profiling of tumor xenografts: in vivo analysis of organ-specific metastasis. Int J Cancer 107(4):528–534PubMedCrossRef

14.

Zhou TT, Zhou P, Yin LH (2006) Crucial role for ecto-5′-nucleotidase (CD73) in invasion and migration of human breast cancer cell lines. Chinese J Pathophysiol 22(2):360–364

15.

Saad S, Gottlieb DJ, Bradstock KF et al (2002) Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts. Cancer Res 62(1):283–289PubMed

16.

Bartsch JE, Staren ED, Appert HE (2003) Adhesion and migration of extracellular matrix-stimulated breast cancer. J Surg Res 110(1):287–294PubMedCrossRef

17.

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

18.

Spychala J, Kitajewski J (2004) Wnt and beta-catenin signaling target the expression of ecto-5′-nucleotidase and increase extracellular adenosine generation. Exp Cell Res 296(2):99–108PubMedCrossRef

19.

Wink MR, Tamajusuku AS, Braganhol E et al (2003) Thyroid hormone upregulates ecto-5′-nucleotidase/CD73 in C6 rat glioma cells. Mol Cell Endocrinol 205(1–2):107–114PubMedCrossRef

20.

El-Darahali A, Fawcett H, Mader JS et al (2005) Adenosine-induced apoptosis in EL-4 thymoma cells is caspase-independent and mediated through a non-classical adenosine receptor. Exp Mol Pathol 79:249–258PubMedCrossRef

21.

Stochaj U, Flocke K, Mathes W et al (1989) 5′-Nucleotidases of chicken gizzard and human pancreatic adenocarcinoma cells are anchored to the plasma membrane via a phosphatidylinositol-glycan. Biochem J 262(1):33–40PubMed

22.

Navarro JM, Olmo N, Turnay J et al (1998) Ecto-5′-nucleotidase from a human colon adenocarcinoma cell line. Correlation between enzyme activity and levels in intact cells. Mol Cell Biochem 187(1–2):121–131PubMedCrossRef

23.

Bianchi V, Spychala J (2003) Mammalian 5′-nucleotidases. J Biol Chem 278(47):46195–46198PubMedCrossRef

24.

Woodhouse EC, Amanatullah DF, Schetz JA et al (1998) Adenosine receptor mediates motility in human melanoma cells. Biochem Biophys Res Commun 246(3):888–894PubMedCrossRef

25.

Othman T, Yan H, Rivkees SA (2003) Oligodendrocytes express functional A1 adenosine receptors that stimulate cellular migration. Glia 44(2):166–172PubMedCrossRef

26.

Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23(11):2445–2459PubMedCrossRef

27.

Hofmann UB, Eggert AA, Blass K et al (2003) Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 63(23):8221–8225PubMed

28.

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. J Cell Biol 136(2):421–431PubMedCrossRef

29.

Olmo N, Turnay J, Risse G et al (1992) Modulation of 5′-nucleotidase activity in plasma membranes and intact cells by the extracellular matrix proteins laminin and fibronectin. Biochem J 282(Pt 1):181–188PubMed

30.

Ioachim E, Charchanti A, Briasoulis E et al (2002) Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer 38(18):2362–2370PubMedCrossRef

31.

Cronstein BN, Levin RI, Philips M et al (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 148(7):2201–2206PubMed

32.

Sadej R, Spychala J, Skladanowski AC (2006) Ecto-5′-nucleotidase (eN, CD73) is coexpressed with metastasis promoting antigens in human melanoma cells. Nucleosides Nucleotides Nucleic Acids 25(9–11):1119–1123PubMedCrossRef

Titel: RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion
verfasst von: Xiuling Zhi
Sifeng Chen
Ping Zhou
Zhimin Shao
Li Wang
Zhouluo Ou
Lianhua Yin
Publikationsdatum: 01.10.2007
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 6/2007
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-007-9081-y

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion

Abstract

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Springer Medizin

Abstract

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