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Sonic Hedgehog Ligand: A Role in Formation of a Mesenchymal Niche in Human Pancreatic Ductal Adenocarcinoma

Saini, Francesca; Argent, Richard H.; Grabowska, Anna

Authors

Francesca Saini

Richard H. Argent

Anna Grabowska



Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterised by desmoplasia, thought to support progression and chemotherapeutic resistance. The Hedgehog pathway is known to play an important role in this cancer. While the upregulation of Sonic hedgehog (Shh) in the epithelium of PDAC is known, we investigated its expression in the tumour microenvironment in order to find new targets for new chemotherapeutical approaches. Immunohistochemistry was used for the investigation of Shh and Vimentin in primary human pancreatic tissues. Gene (qRT-PCR) and protein (immunofluorescence) expression of Shh, αSMA (a marker of the mesenchymal phenotype) and periostin (a marker of mesenchymal cells within a mixed population) were investigated in in vitro cell models. Shh expression was significantly upregulated in the stromal and epithelial compartments of poorly-differentiated PDAC samples, with a strong correlation with the amount of stroma present. Characterisation of stromal cells showed that there was expression of Shh ligand in a mixed population comprising αSMA+ myofibroblasts and αSMA− mesenchymal stem cells. Moreover, we demonstrated the interaction between these cell lines by showing a higher rate of mesenchymal cell proliferation and the upregulation of periostin. Therefore, targeting stromal Shh could affect the equilibrium of the tumour microenvironment and its contribution to tumour growth.

Journal Article Type Article
Publication Date May 8, 2019
Journal Cells
Electronic ISSN 2073-4409
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 8
Issue 5
Article Number 424
Pages 1-15
APA6 Citation Saini, F., Argent, R. H., & Grabowska, A. (2019). Sonic Hedgehog Ligand: A Role in Formation of a Mesenchymal Niche in Human Pancreatic Ductal Adenocarcinoma. Cells, 8(5), 1-15. https://doi.org/10.3390/cells8050424
DOI https://doi.org/10.3390/cells8050424
Keywords pancreatic ductal adenocarcinoma (PDAC); sonic hedgehog (Shh); tumour microenvironment
Publisher URL https://www.mdpi.com/2073-4409/8/5/424

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