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Published in: Tumor Biology 4/2013

01-08-2013 | Research Article

Clinical significance of UNC5B expression in bladder cancer

Authors: Jiao Liu, Zhe Zhang, Zhen-hua Li, Chui-Ze Kong

Published in: Tumor Biology | Issue 4/2013

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Abstract

UNC5B is a membrane-bound receptor of the neural guidance factor netrin-1 family, with important roles in angiogenesis, neurogenesis, embryonic development, cancer, inflammation and various pathologies. However, its effect on bladder cancer has not been reported. To investigate the association of UNC5B expression with bladder cancer prognosis, 100 cases of clinical bladder cancer and adjacent noncancerous tissue samples, and four bladder cancer cell lines were selected using RT-PCR, Western blot, immunofluorescence and immunohistochemistry to investigate differential expression and cellular positioning of UNC5B, and its relationship with clinicopathological parameters. In 72 % of cases, UNC5B was expressed in both bladder cancer and adjacent noncancerous tissue samples. Expression of UNC5B in bladder cancer tissues increased significantly as cancer stage increased (P < 0.05); UNC5B emerged more in bladder cancer cell lines with lower degrees of malignancy than those with higher degrees of malignancy; UNC5B expression in bladder cancer cells was significantly reduced compared to normal bladder cells (P < 0.05). UNC5B mRNA was down-expressed in about 28 % of bladder cancer tissues. Low UNC5B expression was an independent risk factor for postoperative recurrence in patients with different stages and grades bladder cancer. Furthermore, patients with lower UNC5B expression in tumors had significantly higher recurrence rate after curative surgery and poorer prognosis than those with higher UNC5B expression, suggesting that UNC5B could be used to predict prognosis and recurrence.
Literature
1.
go back to reference Jacobs BL, Cheryl T, et al. Bladder cancer in 2010: how far have we come? [J]. CA Cancer J Clin. 2010;60(4):244–72.PubMedCrossRef Jacobs BL, Cheryl T, et al. Bladder cancer in 2010: how far have we come? [J]. CA Cancer J Clin. 2010;60(4):244–72.PubMedCrossRef
2.
3.
go back to reference Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.PubMedCrossRef Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.PubMedCrossRef
4.
go back to reference Laufer M, Ramalingam S, Schoenberg MP, et al. Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: a phase I and pharmacokinetic study. J Clin Oncol. 2003;21(4):697–703.PubMedCrossRef Laufer M, Ramalingam S, Schoenberg MP, et al. Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: a phase I and pharmacokinetic study. J Clin Oncol. 2003;21(4):697–703.PubMedCrossRef
5.
go back to reference Sun CC, Zhang Z, Zhang SY, et al. Up-regulation of glucosylceramide synthase in urinary bladder neoplasms. Urol Oncol. 2012;30(4):444–9. Sun CC, Zhang Z, Zhang SY, et al. Up-regulation of glucosylceramide synthase in urinary bladder neoplasms. Urol Oncol. 2012;30(4):444–9.
6.
go back to reference Julien F, Céline G, Marie-May C, et al. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer. PNAS. 2008;105(12):4850–5.CrossRef Julien F, Céline G, Marie-May C, et al. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer. PNAS. 2008;105(12):4850–5.CrossRef
7.
go back to reference Delloye-Bourgeois C, Brambilla E, Coissieux M-M, et al. Interference with netrin-1 and tumor cell death in non-small cell lung cancer. J Natl Cancer Inst. 2009;101(4):237–47.PubMedCrossRef Delloye-Bourgeois C, Brambilla E, Coissieux M-M, et al. Interference with netrin-1 and tumor cell death in non-small cell lung cancer. J Natl Cancer Inst. 2009;101(4):237–47.PubMedCrossRef
8.
go back to reference Okazaki S, Ishikawa T, Iida S, et al. Clinical significance of UNC5B expression in colorectal cancer. Int J Oncol. 2012;40(1):209–16.PubMed Okazaki S, Ishikawa T, Iida S, et al. Clinical significance of UNC5B expression in colorectal cancer. Int J Oncol. 2012;40(1):209–16.PubMed
9.
go back to reference Céline D-B, Julien F, Andrea P, et al. Netrin-1 acts as a survival factor for aggressive neuroblastoma. J Exp Med. 2009;206(4):833–47.CrossRef Céline D-B, Julien F, Andrea P, et al. Netrin-1 acts as a survival factor for aggressive neuroblastoma. J Exp Med. 2009;206(4):833–47.CrossRef
10.
go back to reference Eble JN, Sauter G, Epstei JI, Sesterhenn IA, editors. World Health Organization classification of tumours. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC Press; 2004. Eble JN, Sauter G, Epstei JI, Sesterhenn IA, editors. World Health Organization classification of tumours. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC Press; 2004.
11.
go back to reference Thomsen R, Solvsten CA, Linnet TE, et al. Analysis of qPCR data by converting exponentially related Ct values into linearly related X0 values. J Bioinform Comput Biol. 2010;8(5):885–900.PubMedCrossRef Thomsen R, Solvsten CA, Linnet TE, et al. Analysis of qPCR data by converting exponentially related Ct values into linearly related X0 values. J Bioinform Comput Biol. 2010;8(5):885–900.PubMedCrossRef
12.
go back to reference Wang R, Wei Z, Jin H, et al. Autoinhibition of UNC5B revealed by the cytoplasmic domain structure of the receptor. Mol Cell. 2009;33(6):692–703.PubMedCrossRef Wang R, Wei Z, Jin H, et al. Autoinhibition of UNC5B revealed by the cytoplasmic domain structure of the receptor. Mol Cell. 2009;33(6):692–703.PubMedCrossRef
13.
go back to reference He K, Jang SW, Joshi J, Yoo MH, et al. Akt-phosphorylated PIKE-A inhibits UNC5B–induced apoptosis in cancer cell lines in a p53-dependent manner. Mol Biol Cell. 2011;22(11):1943–54.PubMedCrossRef He K, Jang SW, Joshi J, Yoo MH, et al. Akt-phosphorylated PIKE-A inhibits UNC5B–induced apoptosis in cancer cell lines in a p53-dependent manner. Mol Biol Cell. 2011;22(11):1943–54.PubMedCrossRef
14.
go back to reference Guenebeaud C, Goldschneider D, Castets M, et al. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol Cell. 2010;40(6):863–76.PubMedCrossRef Guenebeaud C, Goldschneider D, Castets M, et al. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol Cell. 2010;40(6):863–76.PubMedCrossRef
15.
go back to reference Castets M, Coissieux MM, Delloye-Bourgeois C, et al. Mehlen P. Inhibition of endothelial cell apoptosis by netrin-1 during angiogenesis. Dev Cell. 2009;16(4):614–20.PubMedCrossRef Castets M, Coissieux MM, Delloye-Bourgeois C, et al. Mehlen P. Inhibition of endothelial cell apoptosis by netrin-1 during angiogenesis. Dev Cell. 2009;16(4):614–20.PubMedCrossRef
16.
go back to reference Castets M, Mehlen P. Netrin-1 role in angiogenesis: to be or not to be a pro-angiogenic factor? Cell Cycle. 2010;9(8):1466–71.PubMedCrossRef Castets M, Mehlen P. Netrin-1 role in angiogenesis: to be or not to be a pro-angiogenic factor? Cell Cycle. 2010;9(8):1466–71.PubMedCrossRef
17.
go back to reference Han Y, Shao Y, Lin Z, et al. Netrin-1 simultaneously suppresses corneal inflammation and neovascularization. Invest Ophthalmol Vis Sci. 2012;53(3):1285–95.PubMedCrossRef Han Y, Shao Y, Lin Z, et al. Netrin-1 simultaneously suppresses corneal inflammation and neovascularization. Invest Ophthalmol Vis Sci. 2012;53(3):1285–95.PubMedCrossRef
18.
go back to reference Ahmad I, Balasubramanian S, Del Debbio CB, et al. Regulation of ocular angiogenesis by Notch signaling: implications in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(6):2868–78.PubMedCrossRef Ahmad I, Balasubramanian S, Del Debbio CB, et al. Regulation of ocular angiogenesis by Notch signaling: implications in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(6):2868–78.PubMedCrossRef
19.
go back to reference Unoki N, Murakami T, Nishijima K, et al. SDF-1/CXCR4 contributes to the activation of tip cells and microglia in retinal angiogenesis. Invest Ophthalmol Vis Sci. 2010;51(7):3362–71. Unoki N, Murakami T, Nishijima K, et al. SDF-1/CXCR4 contributes to the activation of tip cells and microglia in retinal angiogenesis. Invest Ophthalmol Vis Sci. 2010;51(7):3362–71.
20.
go back to reference Lejmi E, Leconte L, Pédron-Mazoyer S, et al. Netrin-4 inhibits angiogenesis via binding to neogenin and recruitment of UNC5B. Proc Natl Acad Sci U S A. 2008;105(34):12491–6.PubMedCrossRef Lejmi E, Leconte L, Pédron-Mazoyer S, et al. Netrin-4 inhibits angiogenesis via binding to neogenin and recruitment of UNC5B. Proc Natl Acad Sci U S A. 2008;105(34):12491–6.PubMedCrossRef
21.
go back to reference Larrivée B, Freitas C, Trombe M, et al. Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev. 2007;21(19):2433–47.PubMedCrossRef Larrivée B, Freitas C, Trombe M, et al. Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev. 2007;21(19):2433–47.PubMedCrossRef
22.
go back to reference Liu N, Huang H, Lin F, et al. Effects of treadmill exercise on the expression of netrin-1 and its receptors in rat brain after cerebral ischemia. Neuroscience. 2011;194:349–58.PubMedCrossRef Liu N, Huang H, Lin F, et al. Effects of treadmill exercise on the expression of netrin-1 and its receptors in rat brain after cerebral ischemia. Neuroscience. 2011;194:349–58.PubMedCrossRef
23.
go back to reference Zhuang X, Cross D, Heath VL, et al. Shear stress, tip cells and regulators of end othelial migration. Biochem Soc Trans. 2011;39(6):1571–5.PubMedCrossRef Zhuang X, Cross D, Heath VL, et al. Shear stress, tip cells and regulators of end othelial migration. Biochem Soc Trans. 2011;39(6):1571–5.PubMedCrossRef
24.
go back to reference McIntyre JC, Titlow WB, McClintock TS. Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons. J Neurosci Res. 2010;88(15):3243–56.PubMedCrossRef McIntyre JC, Titlow WB, McClintock TS. Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons. J Neurosci Res. 2010;88(15):3243–56.PubMedCrossRef
25.
go back to reference Söllner C, Wright GJ. A cell surface interaction network of neural leucine-rich repeat receptors. Genome Biol. 2009;10(9):R99.PubMedCrossRef Söllner C, Wright GJ. A cell surface interaction network of neural leucine-rich repeat receptors. Genome Biol. 2009;10(9):R99.PubMedCrossRef
26.
go back to reference Tanikawa C, Matsuda K, Fukuda S, et al. Arakawa H. p53RDL1 regulates p53-dependent apoptosis. Nat Cell Biol. 2003;5(3):216–23.PubMedCrossRef Tanikawa C, Matsuda K, Fukuda S, et al. Arakawa H. p53RDL1 regulates p53-dependent apoptosis. Nat Cell Biol. 2003;5(3):216–23.PubMedCrossRef
27.
go back to reference Dakouane-Giudicelli M, Alfaidy N, Bayle P, et al. Hypoxia-inducible factor 1 controls the expression of the uncoordinated-5-B receptor, but not of netrin-1, in first trimester human placenta. Int J Dev Biol. 2011;55(10–12):981–7.PubMedCrossRef Dakouane-Giudicelli M, Alfaidy N, Bayle P, et al. Hypoxia-inducible factor 1 controls the expression of the uncoordinated-5-B receptor, but not of netrin-1, in first trimester human placenta. Int J Dev Biol. 2011;55(10–12):981–7.PubMedCrossRef
28.
go back to reference Dakouane-Giudicelli M, Duboucher C, Fortemps J, et al. Characterization and express ion of netrin-1 and its receptors UNC5B and DCC in human placenta. J Histochem Cytochem. 2010;58(1):73–82.PubMedCrossRef Dakouane-Giudicelli M, Duboucher C, Fortemps J, et al. Characterization and express ion of netrin-1 and its receptors UNC5B and DCC in human placenta. J Histochem Cytochem. 2010;58(1):73–82.PubMedCrossRef
29.
go back to reference Karaulanov E, Böttcher RT, Stannek P, et al. UNC5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus embryos. PLoS One. 2009;4(5):e5742.PubMedCrossRef Karaulanov E, Böttcher RT, Stannek P, et al. UNC5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus embryos. PLoS One. 2009;4(5):e5742.PubMedCrossRef
30.
go back to reference Navankasattusas S, Whitehead KJ, Suli A, et al. The netrin receptor UNC5B promotes angiogenesis in specific vascular beds. Development. 2008;135(4):659–67.PubMedCrossRef Navankasattusas S, Whitehead KJ, Suli A, et al. The netrin receptor UNC5B promotes angiogenesis in specific vascular beds. Development. 2008;135(4):659–67.PubMedCrossRef
31.
go back to reference Thiebault K, Mazelin L, Pays L, et al. The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment. Proc Natl Acad Sci U S A. 2003;100(7):4173–8.PubMedCrossRef Thiebault K, Mazelin L, Pays L, et al. The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment. Proc Natl Acad Sci U S A. 2003;100(7):4173–8.PubMedCrossRef
32.
go back to reference Zhang H, Wu F, Tao YM, et al. Down-regulated expression of UNC5B related to hepatocellular carcinoma angiogenesis. Zhonghua Wai Ke Za Zhi. 2009;47(20):1569–73.PubMed Zhang H, Wu F, Tao YM, et al. Down-regulated expression of UNC5B related to hepatocellular carcinoma angiogenesis. Zhonghua Wai Ke Za Zhi. 2009;47(20):1569–73.PubMed
33.
go back to reference Linden J. Regulation of leukocyte function by adenosine receptors. Adv Pharmacol. 2011;61:95–114.PubMedCrossRef Linden J. Regulation of leukocyte function by adenosine receptors. Adv Pharmacol. 2011;61:95–114.PubMedCrossRef
34.
go back to reference Hata K, Kaibuchi K, Inagaki S, et al. UNC5B associates with LARG to mediate the action of repulsive guidance molecule. J Cell Biol. 2009;184(5):737–50.PubMedCrossRef Hata K, Kaibuchi K, Inagaki S, et al. UNC5B associates with LARG to mediate the action of repulsive guidance molecule. J Cell Biol. 2009;184(5):737–50.PubMedCrossRef
Metadata
Title
Clinical significance of UNC5B expression in bladder cancer
Authors
Jiao Liu
Zhe Zhang
Zhen-hua Li
Chui-Ze Kong
Publication date
01-08-2013
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2013
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0532-y

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