Skip to main content
Erschienen in: Tumor Biology 4/2014

01.04.2014 | Research Article

Strong claudin 5 expression is a poor prognostic sign in pancreatic adenocarcinoma

verfasst von: Ylermi Soini, M. Eskelinen, P. Juvonen, V. Kärjä, K. M. Haapasaari, A. Saarela, P. Karihtala

Erschienen in: Tumor Biology | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

We investigated the expression of claudin 5 in 88 ductal adenocarcinomas of the pancreas. The results were correlated with patient prognosis, with claudin 5 expression in blood vessels, with the expression level of bcl2 and bax and with apoptosis. Claudin 5 expression was detected in 24 (38 %) cases. It was not associated with tumour size or spread, but strong claudin 5 expression correlated with a worse survival (p = 0.005). Claudin 5 also associated with a higher extent of apoptosis and greater expression of bax protein. In the tumour vasculature, some vessels displayed a loss of claudin 5 expression. The presence of this loss was associated with tumour grade and the presence of nodal metastases (p = 0.02, p = 0.022, respectively). These results indicate that claudin 5 is upregulated in a proportion of pancreatic ductal adenocarcinomas. The association of strong claudin 5 expression with a worse survival is in line with some earlier reports indicating that this protein is involved with increased locomotion and more aggressive spread of carcinomas. The association of claudin 5 with apoptosis and bax might be due to stronger cellular kinetics found in such tumours. The loss of claudin 5 expression in the tumour vasculature points to a leaky vessel type; this might also ease the access of tumours to vessels and be reflected in its association with the presence of nodal metastases.
Literatur
1.
Zurück zum Zitat Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J, Blasig IE. Structure and function of claudins. Biochim Biophys Acta. 2008;1778:631–45.PubMedCrossRef Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J, Blasig IE. Structure and function of claudins. Biochim Biophys Acta. 2008;1778:631–45.PubMedCrossRef
2.
Zurück zum Zitat Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, et al. Tight junctions and human diseases. Med Electron Microsc. 2003;36:147–56.PubMedCrossRef Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, et al. Tight junctions and human diseases. Med Electron Microsc. 2003;36:147–56.PubMedCrossRef
3.
Zurück zum Zitat Mineta K, Yamamoto Y, Yamazaki Y, Tanaka H, Tada Y, Saito K, et al. Predicted expansion of the claudin multigene family. FEBS Lett. 2011;585:606–12.PubMedCrossRef Mineta K, Yamamoto Y, Yamazaki Y, Tanaka H, Tada Y, Saito K, et al. Predicted expansion of the claudin multigene family. FEBS Lett. 2011;585:606–12.PubMedCrossRef
4.
Zurück zum Zitat Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wölk B, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007;446:801–5.PubMedCrossRef Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wölk B, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007;446:801–5.PubMedCrossRef
5.
Zurück zum Zitat Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999;147:185–94.PubMedCentralPubMedCrossRef Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999;147:185–94.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Morrow CM, Tyagi G, Simon L, Carnes K, Murphy KM, Cooke PS, et al. Claudin 5 expression in mouse seminiferous epithelium is dependent upon the transcription factor ets variant 5 and contributes to blood-testis barrier function. Biol Reprod. 2009;81:871–9.PubMedCentralPubMedCrossRef Morrow CM, Tyagi G, Simon L, Carnes K, Murphy KM, Cooke PS, et al. Claudin 5 expression in mouse seminiferous epithelium is dependent upon the transcription factor ets variant 5 and contributes to blood-testis barrier function. Biol Reprod. 2009;81:871–9.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, et al. Size-selective loosening of the blood–brain barrier in claudin-5-deficient mice. J Cell Biol. 2003;161:653–60.PubMedCentralPubMedCrossRef Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, et al. Size-selective loosening of the blood–brain barrier in claudin-5-deficient mice. J Cell Biol. 2003;161:653–60.PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology. 2005;46:551–60.PubMedCrossRef Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology. 2005;46:551–60.PubMedCrossRef
9.
Zurück zum Zitat Turunen M, Talvensaari-Mattila A, Soini Y, Santala M. Claudin-5 overexpression correlates with aggressive behavior in serous ovarian adenocarcinoma. Anticancer Res. 2009;29:5185–9.PubMed Turunen M, Talvensaari-Mattila A, Soini Y, Santala M. Claudin-5 overexpression correlates with aggressive behavior in serous ovarian adenocarcinoma. Anticancer Res. 2009;29:5185–9.PubMed
10.
Zurück zum Zitat Escudero-Esparza A, Jiang WG, Martin TA. Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways. J Exp Clin Cancer Res. 2012;31:43.PubMedCentralPubMedCrossRef Escudero-Esparza A, Jiang WG, Martin TA. Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways. J Exp Clin Cancer Res. 2012;31:43.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Rahner C, Mitic LL, Anderson JM. Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology. 2001;120:411–22.PubMedCrossRef Rahner C, Mitic LL, Anderson JM. Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology. 2001;120:411–22.PubMedCrossRef
12.
Zurück zum Zitat Comper F, Antonello D, Beghelli S, Gobbo S, Montagna L, Pederzoli P, et al. Expression pattern of claudins 5 and 7 distinguishes solid-pseudopapillary from pancreatoblastoma, acinar cell and endocrine tumors of the pancreas. Am J Surg Pathol. 2009;33:768–74.PubMedCrossRef Comper F, Antonello D, Beghelli S, Gobbo S, Montagna L, Pederzoli P, et al. Expression pattern of claudins 5 and 7 distinguishes solid-pseudopapillary from pancreatoblastoma, acinar cell and endocrine tumors of the pancreas. Am J Surg Pathol. 2009;33:768–74.PubMedCrossRef
13.
Zurück zum Zitat Karanjawala ZE, Illei PB, Ashfaq R, Infante JR, Murphy K, Pandey A, et al. New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. Am J Surg Pathol. 2008;32:188–96.PubMedCentralPubMedCrossRef Karanjawala ZE, Illei PB, Ashfaq R, Infante JR, Murphy K, Pandey A, et al. New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. Am J Surg Pathol. 2008;32:188–96.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Tsukahara M, Nagai H, Kamiakito T, Kawata H, Takayashiki N, Saito K, et al. Distinct expression patterns of claudin-1 and claudin-4 in intraductal papillary-mucinous tumors of the pancreas. Pathol Int. 2005;55:63–9.PubMedCrossRef Tsukahara M, Nagai H, Kamiakito T, Kawata H, Takayashiki N, Saito K, et al. Distinct expression patterns of claudin-1 and claudin-4 in intraductal papillary-mucinous tumors of the pancreas. Pathol Int. 2005;55:63–9.PubMedCrossRef
15.
Zurück zum Zitat Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Lyon: IARC; 2009. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Lyon: IARC; 2009.
16.
Zurück zum Zitat Szasz AM, Tokes AM, Micsinai M, Krenacs T, Jakab C, Lukacs L, et al. Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis. Clin Exp Metastasis. 2011;28:55–63.PubMedCrossRef Szasz AM, Tokes AM, Micsinai M, Krenacs T, Jakab C, Lukacs L, et al. Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis. Clin Exp Metastasis. 2011;28:55–63.PubMedCrossRef
17.
Zurück zum Zitat Korompay A, Borka K, Lotz G, Somorácz A, Törzsök P, Erdélyi-Belle B, et al. Tricellulin expression in normal and neoplastic human pancreas. Histopathology. 2012;60:E76–86.PubMedCrossRef Korompay A, Borka K, Lotz G, Somorácz A, Törzsök P, Erdélyi-Belle B, et al. Tricellulin expression in normal and neoplastic human pancreas. Histopathology. 2012;60:E76–86.PubMedCrossRef
18.
Zurück zum Zitat Liu T, Sun B, Zhao X, Gu Q, Dong X, Yao Z, et al. HER2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma. J Cell Mol Med. 2013;17:116–22.PubMedCrossRef Liu T, Sun B, Zhao X, Gu Q, Dong X, Yao Z, et al. HER2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma. J Cell Mol Med. 2013;17:116–22.PubMedCrossRef
19.
Zurück zum Zitat Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, et al. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 2008;10:923–34.PubMedCrossRef Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, et al. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 2008;10:923–34.PubMedCrossRef
20.
Zurück zum Zitat Ping YF, Bian XW. Concise review: contribution of cancer stem cells to neovascularization. Stem Cells. 2011;29:888–94.PubMedCrossRef Ping YF, Bian XW. Concise review: contribution of cancer stem cells to neovascularization. Stem Cells. 2011;29:888–94.PubMedCrossRef
21.
Zurück zum Zitat Jouppila-Mättö A, Närkiö-Mäkelä M, Soini Y, Pukkila M, Sironen R, Tuhkanen H, et al. Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression. BMC Cancer. 2011;11:350.PubMedCentralPubMedCrossRef Jouppila-Mättö A, Närkiö-Mäkelä M, Soini Y, Pukkila M, Sironen R, Tuhkanen H, et al. Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression. BMC Cancer. 2011;11:350.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Watabe T, Miyazono K. Snail is required for TGF beta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J Cell Sci. 2008;121:3317–24.PubMedCrossRef Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Watabe T, Miyazono K. Snail is required for TGF beta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J Cell Sci. 2008;121:3317–24.PubMedCrossRef
23.
Zurück zum Zitat Soini Y, Tommola S, Helin H, Martikainen P. Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch. 2006;448:52–8.PubMedCrossRef Soini Y, Tommola S, Helin H, Martikainen P. Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch. 2006;448:52–8.PubMedCrossRef
Metadaten
Titel
Strong claudin 5 expression is a poor prognostic sign in pancreatic adenocarcinoma
verfasst von
Ylermi Soini
M. Eskelinen
P. Juvonen
V. Kärjä
K. M. Haapasaari
A. Saarela
P. Karihtala
Publikationsdatum
01.04.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1503-7

Weitere Artikel der Ausgabe 4/2014

Tumor Biology 4/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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