Skip to main content
Erschienen in: Medical Oncology 4/2015

01.04.2015 | Original Paper

Wnt2 protein plays a role in the progression of pancreatic cancer promoted by pancreatic stellate cells

verfasst von: Yong Xu, Hua Li, Chongbiao Huang, Tiansuo Zhao, Huan Zhang, Chen Zheng, He Ren, Jihui Hao

Erschienen in: Medical Oncology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

This study aimed to investigate the expression of Wnt2 protein in pancreatic cancer tissues and pancreatic stellate cells (PSCs), and determine its effect on the biological functions of pancreatic cancer cells. Immunohistochemistry was used to study the expression pattern of Wnt2 in pancreatic cancer tissues. The relationship between Wnt2 protein expression level and patient prognosis was analyzed. PSCs were isolated and cultured. The expression of Wnt2 in activated PSCs was investigated using Western blot and immunofluorescence. We also analyzed the effect of Wnt2 recombinant protein and stellate cell culture supernatant on the Wnt/β-catenin signaling pathway, as well as the effect of Wnt2 recombinant protein on the biological functions of pancreatic cancer cells. The expression of Wnt2 in interstitial cells of pancreatic cancer was correlated with the prognosis of pancreatic cancer. Wnt2 protein was expressed in activated PSCs. Both stellate cell culture supernatant and Wnt2 recombinant protein could activate the classic Wnt/β-catenin signaling pathway. Wnt2 protein enhanced the migration, invasion, and metastasis of pancreatic cancer cells. These results suggested that Wnt2 protein secreted by PSCs promoted the progression of pancreatic cancer by activating the classic Wnt/β-catenin signaling pathway.
Literatur
1.
Zurück zum Zitat Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011. CA Cancer J Clin. 2011;61(4):212–36.CrossRefPubMed Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011. CA Cancer J Clin. 2011;61(4):212–36.CrossRefPubMed
2.
Zurück zum Zitat Mario AS, Surabhi D-G, Amanda JR, Hidayatullah GM. Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J. 2012;441(2):541–52.CrossRef Mario AS, Surabhi D-G, Amanda JR, Hidayatullah GM. Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J. 2012;441(2):541–52.CrossRef
3.
Zurück zum Zitat Bachem MG, Schneider E, Groß H, Weidenbach H, Schmid RM, Menke A, et al. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 1998;115(2):421–32.CrossRefPubMed Bachem MG, Schneider E, Groß H, Weidenbach H, Schmid RM, Menke A, et al. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 1998;115(2):421–32.CrossRefPubMed
4.
Zurück zum Zitat Froeling FE, Mirza TA, Feakins RM, Seedhar A, Elia G, Hart IR, et al. Organotypic culture model of pancreatic cancer demonstrates that stromal cells modulate E-cadherin, β-catenin, and Ezrin expression in tumor cells. Am J Pathol. 2009;175(2):636–48.CrossRefPubMedCentralPubMed Froeling FE, Mirza TA, Feakins RM, Seedhar A, Elia G, Hart IR, et al. Organotypic culture model of pancreatic cancer demonstrates that stromal cells modulate E-cadherin, β-catenin, and Ezrin expression in tumor cells. Am J Pathol. 2009;175(2):636–48.CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat Jiang H, Li Q, He C, Li F, Sheng H, Shen X, et al. Activation of the Wnt pathway through Wnt2 promotes metastasis in pancreatic cancer. Am J Cancer Res. 2014;4(5):537.PubMedCentralPubMed Jiang H, Li Q, He C, Li F, Sheng H, Shen X, et al. Activation of the Wnt pathway through Wnt2 promotes metastasis in pancreatic cancer. Am J Cancer Res. 2014;4(5):537.PubMedCentralPubMed
7.
Zurück zum Zitat Fu L, Zhang C, Zhang L-Y, Dong S-S, Lu L-H, Chen J, et al. Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway. Gut. 2011;60(12):1635–43.CrossRefPubMed Fu L, Zhang C, Zhang L-Y, Dong S-S, Lu L-H, Chen J, et al. Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway. Gut. 2011;60(12):1635–43.CrossRefPubMed
8.
Zurück zum Zitat Hu Y, Wan R, Yu G, Shen J, Ni J, Yin G, et al. Imbalance of Wnt/Dkk negative feedback promotes persistent activation of pancreatic stellate cells in chronic pancreatitis. PLoS One. 2014;9(4):e95145.CrossRefPubMedCentralPubMed Hu Y, Wan R, Yu G, Shen J, Ni J, Yin G, et al. Imbalance of Wnt/Dkk negative feedback promotes persistent activation of pancreatic stellate cells in chronic pancreatitis. PLoS One. 2014;9(4):e95145.CrossRefPubMedCentralPubMed
10.
Zurück zum Zitat Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A, et al. Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 2008;68(3):918–26.CrossRefPubMedCentralPubMed Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A, et al. Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 2008;68(3):918–26.CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Erkan M, Reiser-Erkan C, Michalski CW, Deucker S, Sauliunaite D, Streit S, et al. Cancer-stellate cell interactions perpetuate the hypoxia-fibrosis cycle in pancreatic ductal adenocarcinoma. Neoplasia. 2009;11(5):497–508.PubMedCentralPubMed Erkan M, Reiser-Erkan C, Michalski CW, Deucker S, Sauliunaite D, Streit S, et al. Cancer-stellate cell interactions perpetuate the hypoxia-fibrosis cycle in pancreatic ductal adenocarcinoma. Neoplasia. 2009;11(5):497–508.PubMedCentralPubMed
12.
Zurück zum Zitat Vonlaufen A, Joshi S, Qu C, Phillips PA, Xu Z, Parker NR, et al. Pancreatic stellate cells: partners in crime with pancreatic cancer cells. Cancer Res. 2008;68(7):2085–93.CrossRefPubMed Vonlaufen A, Joshi S, Qu C, Phillips PA, Xu Z, Parker NR, et al. Pancreatic stellate cells: partners in crime with pancreatic cancer cells. Cancer Res. 2008;68(7):2085–93.CrossRefPubMed
13.
Zurück zum Zitat Froeling FE, Feig C, Chelala C, Dobson R, Mein CE, Tuveson DA, et al. Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt–β-catenin signaling to slow tumor progression. Gastroenterology. 2011;141(4):1486–97 e14.CrossRefPubMed Froeling FE, Feig C, Chelala C, Dobson R, Mein CE, Tuveson DA, et al. Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt–β-catenin signaling to slow tumor progression. Gastroenterology. 2011;141(4):1486–97 e14.CrossRefPubMed
14.
Zurück zum Zitat Wells JM, Esni F, Boivin GP, Aronow BJ, Stuart W, Combs C, et al. Wnt/β-catenin signaling is required for development of the exocrine pancreas. BMC Dev Biol. 2007;7(1):4.CrossRefPubMedCentralPubMed Wells JM, Esni F, Boivin GP, Aronow BJ, Stuart W, Combs C, et al. Wnt/β-catenin signaling is required for development of the exocrine pancreas. BMC Dev Biol. 2007;7(1):4.CrossRefPubMedCentralPubMed
15.
Zurück zum Zitat Zhang Y, Morris JP, Yan W, Schofield HK, Gurney A, Simeone DM, et al. Canonical Wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 2013;73(15):4909–22.CrossRefPubMedCentralPubMed Zhang Y, Morris JP, Yan W, Schofield HK, Gurney A, Simeone DM, et al. Canonical Wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 2013;73(15):4909–22.CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Morris JP, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010;10(10):683–95.CrossRefPubMedCentralPubMed Morris JP, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010;10(10):683–95.CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Park J, Song J, He T, Nam S, Lee J, Park W. Overexpression of Wnt-2 in colorectal cancers. Neoplasma. 2008;56(2):119–23.CrossRef Park J, Song J, He T, Nam S, Lee J, Park W. Overexpression of Wnt-2 in colorectal cancers. Neoplasma. 2008;56(2):119–23.CrossRef
Metadaten
Titel
Wnt2 protein plays a role in the progression of pancreatic cancer promoted by pancreatic stellate cells
verfasst von
Yong Xu
Hua Li
Chongbiao Huang
Tiansuo Zhao
Huan Zhang
Chen Zheng
He Ren
Jihui Hao
Publikationsdatum
01.04.2015
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 4/2015
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-015-0513-2

Weitere Artikel der Ausgabe 4/2015

Medical Oncology 4/2015 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.