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Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion.

Franco R, Zappavigna S, Gigantino V, Luce A, Cantile M, Cerrone M, Facchini G, Perdonà S, Pignata S, Di Lorenzo G, Chieffi S, Vitale G, De Sio M, Sgambato A, Botti G, Yousif AM, Novellino E, Grieco P, Caraglia M - J. Exp. Clin. Cancer Res. (2014)

Bottom Line: UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC.Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. michele.caraglia@unina2.it.

ABSTRACT

Background: Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.

Methods: We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.

Results: UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.

Conclusions: The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

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Immunohistochemical UTR expression in NMIBC. A, A1): High UTR expression (20x, 40x) in a patient without recurrence; B, B1): low UTR expression (20×, 40×) in a patient with recurrence.
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Figure 2: Immunohistochemical UTR expression in NMIBC. A, A1): High UTR expression (20x, 40x) in a patient without recurrence; B, B1): low UTR expression (20×, 40×) in a patient with recurrence.

Mentions: High-grade primitive tumours have been observed in 41 patients (26%); the relapse tumor grade was the same of primitive tumors in 71 cases (94%), while 4 cases (6%) of the relapsed tumours showed higher grade than the primary. In 53 cases (33%) lamina propria infiltration was observed (Table 1).High expression was recorded when positive cells were > 30%. Patients with low expression of UTR were 94 (59%), in particular 38 (40%) without recurrences and 56 (60%) with histologically documented recurrences. Moreover, 65 patients (41%) showed high expression of UTR, 46 (71%) without recurrences and 19 (29%) with recurrences. High UTR expression was significantly associated to low grade carcinoma (p = 0.044) while low expression was associated to cases that have developed at least one relapse (p = 0.001). Moreover, UTR expression in relapses was significantly lost respect to primary tumors (p = 0.025) (Figures 2 and3).


Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion.

Franco R, Zappavigna S, Gigantino V, Luce A, Cantile M, Cerrone M, Facchini G, Perdonà S, Pignata S, Di Lorenzo G, Chieffi S, Vitale G, De Sio M, Sgambato A, Botti G, Yousif AM, Novellino E, Grieco P, Caraglia M - J. Exp. Clin. Cancer Res. (2014)

Immunohistochemical UTR expression in NMIBC. A, A1): High UTR expression (20x, 40x) in a patient without recurrence; B, B1): low UTR expression (20×, 40×) in a patient with recurrence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4061920&req=5

Figure 2: Immunohistochemical UTR expression in NMIBC. A, A1): High UTR expression (20x, 40x) in a patient without recurrence; B, B1): low UTR expression (20×, 40×) in a patient with recurrence.
Mentions: High-grade primitive tumours have been observed in 41 patients (26%); the relapse tumor grade was the same of primitive tumors in 71 cases (94%), while 4 cases (6%) of the relapsed tumours showed higher grade than the primary. In 53 cases (33%) lamina propria infiltration was observed (Table 1).High expression was recorded when positive cells were > 30%. Patients with low expression of UTR were 94 (59%), in particular 38 (40%) without recurrences and 56 (60%) with histologically documented recurrences. Moreover, 65 patients (41%) showed high expression of UTR, 46 (71%) without recurrences and 19 (29%) with recurrences. High UTR expression was significantly associated to low grade carcinoma (p = 0.044) while low expression was associated to cases that have developed at least one relapse (p = 0.001). Moreover, UTR expression in relapses was significantly lost respect to primary tumors (p = 0.025) (Figures 2 and3).

Bottom Line: UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC.Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. michele.caraglia@unina2.it.

ABSTRACT

Background: Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.

Methods: We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.

Results: UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.

Conclusions: The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

Show MeSH
Related in: MedlinePlus