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World J Gastroenterol. Aug 28, 2014; 20(32): 11216-11229
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11216
Pancreatic cancer and its stroma: A conspiracy theory
Zhihong Xu, Srinivasa P Pothula, Jeremy S Wilson, Minoti V Apte
Zhihong Xu, Srinivasa P Pothula, Jeremy S Wilson, Minoti V Apte, Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2170, Australia
Zhihong Xu, Srinivasa P Pothula, Jeremy S Wilson, Minoti V Apte, Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia
Author contributions: Xu Z and Apte MV wrote the paper; Xu Z, Pothula SP, Wilson JS and Apte MV revised the paper.
Supported by National Health and Medical Research Council of Australia, the Cancer Council of New South Wales and the Cancer Institute NSW
Correspondence to: Minoti V Apte, Professor, Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Liverpool, Sydney, NSW 2170, Australia. m.apte@unsw.edu.au
Telephone: +61-2-87389029 Fax: +61-2-96029441
Received: November 4, 2013
Revised: February 18, 2014
Accepted: April 15, 2014
Published online: August 28, 2014
Abstract

Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

Keywords: Pancreatic cancer, Stromal reaction, Tumour-stroma interactions, Pancreatic stellate cells, Metastasis

Core tip: This review summarises current knowledge about the role of pancreatic stellate cells in production of cancer stroma, the mechanisms mediating stromal-tumour interactions and novel therapeutic approaches developed on the basis of our increasing understanding of the critical influence of stromal elements on disease progression.