Skip to main content
Erschienen in: Tumor Biology 4/2013

01.08.2013 | Research Article

Clinical significance of UNC5B expression in bladder cancer

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

Erschienen in: Tumor Biology | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef
3.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Clinical significance of UNC5B expression in bladder cancer
verfasst von
Jiao Liu
Zhe Zhang
Zhen-hua Li
Chui-Ze Kong
Publikationsdatum
01.08.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0532-y

Weitere Artikel der Ausgabe 4/2013

Tumor Biology 4/2013 Zur Ausgabe

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.