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CCL20/CCR6 expression profile in pancreatic cancer.

Rubie C, Frick VO, Ghadjar P, Wagner M, Grimm H, Vicinus B, Justinger C, Graeber S, Schilling MK - J Transl Med (2010)

Bottom Line: Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05).CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively).CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of General -, Visceral-, Vascular - and Paediatric Surgery, University of the Saarland, Homburg/Saar, Germany. claudia.rubie@uks.eu

ABSTRACT

Background: CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated.

Methods: Using RealTime-PCR, enzyme-linked immunosorbent assay (ELISA), Western Blot and immunohistochemistry, we have analyzed the expression profile of CCL20/CCR6 in resection specimens from patients with chronic pancreatitis (CP) (n = 22), pancreatic cystadenoma (PA) (n = 11) and pancreatic carcinoma (PCA) (n = 25) as well as in the respective matched normal pancreatic tissues.

Results: CCL20 mRNA and protein was weakly expressed in normal pancreatic tissues and CP and PA specimens but significantly up-regulated in PCA (8-fold) as compared to the matched normal tissue (P < 0.05). Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05). CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively).

Conclusion: CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients. This suggests that CCL20 and CCR6 play a role in the development and progression of PCA and may constitute potential targets for novel treatment strategies.

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Results of anti-CCL20 immunohistochemistry in normal and diseased pancreatic tissues. Representative example of CCL20 expression in [A,B] pancreatic islet cells and epithelial cells of pancreatic ducts, [C] necrotic parenchyma and epithelial cells of pancreatic ducts in chronic pancreatitis tissues [D] epithelial cells of the characteristic net-like structures of pancreatic cystadenoma [E,F] cytoplasms of ductal epithelial cancer cells and in infiltrates of perineural sheaths. Anti-CCL20 goat anti-human, 75 μg/ml (MIP-3α; R&D Systems; Minneapolis, MN, USA. Avidin Biotin Complex (ABC) Method. (original magnification: × 200 and 400, respectively).
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Figure 3: Results of anti-CCL20 immunohistochemistry in normal and diseased pancreatic tissues. Representative example of CCL20 expression in [A,B] pancreatic islet cells and epithelial cells of pancreatic ducts, [C] necrotic parenchyma and epithelial cells of pancreatic ducts in chronic pancreatitis tissues [D] epithelial cells of the characteristic net-like structures of pancreatic cystadenoma [E,F] cytoplasms of ductal epithelial cancer cells and in infiltrates of perineural sheaths. Anti-CCL20 goat anti-human, 75 μg/ml (MIP-3α; R&D Systems; Minneapolis, MN, USA. Avidin Biotin Complex (ABC) Method. (original magnification: × 200 and 400, respectively).

Mentions: Using immunohistochemistry CP, PA and PCA specimens along with the corresponding normal tissues were evaluated for CCL20 expression (Figure 3). CCL20 signals were detected in all CP, PA and PCA specimens under investigation. In normal tissues, CCL20 staining was primarily found in pancreatic islet cells and rather sporadically in epithelial cells of pancreatic ducts as shown in Figure 3A and 3B. In CP tissues immunoreactive CCL20 signals were detected primarily in acinar parenchyma deformed by necrosis and sporadically in some epithelial cells of pancreatic ducts (Figure 3C). Likewise, CCL20 staining was found in epithelial cells of the characteristic net-like structures of PA tissues (Figure 3D). In PCA tissues CCL20 immunoreactivity was detected in the cytoplasms of ductal epithelial cancer cells (Figure 3E). Moreover, CCL20 signals were detected in infiltrates of perineural sheaths as shown in Figure 3F.


CCL20/CCR6 expression profile in pancreatic cancer.

Rubie C, Frick VO, Ghadjar P, Wagner M, Grimm H, Vicinus B, Justinger C, Graeber S, Schilling MK - J Transl Med (2010)

Results of anti-CCL20 immunohistochemistry in normal and diseased pancreatic tissues. Representative example of CCL20 expression in [A,B] pancreatic islet cells and epithelial cells of pancreatic ducts, [C] necrotic parenchyma and epithelial cells of pancreatic ducts in chronic pancreatitis tissues [D] epithelial cells of the characteristic net-like structures of pancreatic cystadenoma [E,F] cytoplasms of ductal epithelial cancer cells and in infiltrates of perineural sheaths. Anti-CCL20 goat anti-human, 75 μg/ml (MIP-3α; R&D Systems; Minneapolis, MN, USA. Avidin Biotin Complex (ABC) Method. (original magnification: × 200 and 400, respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2877001&req=5

Figure 3: Results of anti-CCL20 immunohistochemistry in normal and diseased pancreatic tissues. Representative example of CCL20 expression in [A,B] pancreatic islet cells and epithelial cells of pancreatic ducts, [C] necrotic parenchyma and epithelial cells of pancreatic ducts in chronic pancreatitis tissues [D] epithelial cells of the characteristic net-like structures of pancreatic cystadenoma [E,F] cytoplasms of ductal epithelial cancer cells and in infiltrates of perineural sheaths. Anti-CCL20 goat anti-human, 75 μg/ml (MIP-3α; R&D Systems; Minneapolis, MN, USA. Avidin Biotin Complex (ABC) Method. (original magnification: × 200 and 400, respectively).
Mentions: Using immunohistochemistry CP, PA and PCA specimens along with the corresponding normal tissues were evaluated for CCL20 expression (Figure 3). CCL20 signals were detected in all CP, PA and PCA specimens under investigation. In normal tissues, CCL20 staining was primarily found in pancreatic islet cells and rather sporadically in epithelial cells of pancreatic ducts as shown in Figure 3A and 3B. In CP tissues immunoreactive CCL20 signals were detected primarily in acinar parenchyma deformed by necrosis and sporadically in some epithelial cells of pancreatic ducts (Figure 3C). Likewise, CCL20 staining was found in epithelial cells of the characteristic net-like structures of PA tissues (Figure 3D). In PCA tissues CCL20 immunoreactivity was detected in the cytoplasms of ductal epithelial cancer cells (Figure 3E). Moreover, CCL20 signals were detected in infiltrates of perineural sheaths as shown in Figure 3F.

Bottom Line: Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05).CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively).CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of General -, Visceral-, Vascular - and Paediatric Surgery, University of the Saarland, Homburg/Saar, Germany. claudia.rubie@uks.eu

ABSTRACT

Background: CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated.

Methods: Using RealTime-PCR, enzyme-linked immunosorbent assay (ELISA), Western Blot and immunohistochemistry, we have analyzed the expression profile of CCL20/CCR6 in resection specimens from patients with chronic pancreatitis (CP) (n = 22), pancreatic cystadenoma (PA) (n = 11) and pancreatic carcinoma (PCA) (n = 25) as well as in the respective matched normal pancreatic tissues.

Results: CCL20 mRNA and protein was weakly expressed in normal pancreatic tissues and CP and PA specimens but significantly up-regulated in PCA (8-fold) as compared to the matched normal tissue (P < 0.05). Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05). CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively).

Conclusion: CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients. This suggests that CCL20 and CCR6 play a role in the development and progression of PCA and may constitute potential targets for novel treatment strategies.

Show MeSH
Related in: MedlinePlus