MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer.

Karamitopoulou, Evanthia; Haemmig, Stefan; Baumgartner, Ulrich; Schlup, Cornelia; Wartenberg, Martin; Vassella, Erik (2017). MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer. Modern pathology, 30(8), pp. 1116-1125. Nature Publishing Group 10.1038/modpathol.2017.35

[img] Text
modpathol201735.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (599kB) | Request a copy

Cellular interactions in the tumor microenvironment influence neoplastic progression in pancreatic ductal adenocarcinoma. One underlying mechanism is the induction of the prognostically unfavorable epithelial-mesenchymal-transition-like tumor budding. Our aim is to explore the expression of microRNAs implicated in the regulation of tumor budding focusing on the microenvironment of the invasive front. To this end, RNA from laser-capture-microdissected material of the main tumor, tumor buds, juxta-tumoral stroma, tumor-remote stroma, and non-neoplastic pancreatic parenchyma from pancreatic cancer cases with (n=7) and without (n=6) tumor budding was analyzed by qRT-PCR for the expression of a panel of miRNAs that are known to be implicated in the regulation of epithelial-mesenchymal transition, including miR-21, miR-183, miR-200b, miR-200c, miR-203, miR-205, miR-210, and miR-217. Here we show that at the invasive front of pancreatic ductal adenocarcinoma, specific microRNAs, are differentially expressed between tumor buds and main tumor cells and between cases with and without tumor budding, indicating their involvement in the regulation of the budding phenotype. Notably, miR-200b and miR-200c were significantly downregulated in the tumor buds. Consistent with this finding, they negatively correlated with the expression of epithelial-mesenchymal-transition-associated E-cadherin repressors ZEB1 and ZEB2 in the budding cells (P<0.001). Interestingly, many microRNAs were also dysregulated in juxta-tumoral compared to tumor-remote stroma suggesting that juxta-tumoral stroma contributes to microRNA dysregulation. Notably, miR-200b and miR-200c were strongly downregulated while miR-210 and miR-21 were upregulated in the juxta-tumoral vs tumor-remote stroma in carcinomas with tumor budding. In conclusion, microRNA targeting in both tumor and stromal cells could represent a treatment option for aggressive pancreatic cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Molecular Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

UniBE Contributor:

Karamitopoulou, Evanthia; Haemmig, Stefan; Baumgartner, Ulrich; Schlup, Cornelia and Vassella, Erik

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0893-3952

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Erik Vassella-Zürcher

Date Deposited:

16 Nov 2017 08:19

Last Modified:

16 Nov 2017 08:27

Publisher DOI:

10.1038/modpathol.2017.35

PubMed ID:

28548126

BORIS DOI:

10.7892/boris.107110

URI:

https://boris.unibe.ch/id/eprint/107110

Actions (login required)

Edit item Edit item
Provide Feedback