Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

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Apr 9, 2014 - Group, Lowy Cancer Research. Centre, Prince of Wales Clinical. School, University of New South. Wales, High St., Randwick, Sydney,. NSW ...
REVIEW ARTICLE published: 09 April 2014 doi: 10.3389/fphys.2014.00141

Role of pancreatic stellate cells in chemoresistance in pancreatic cancer Joshua A. McCarroll 1,2† , Stephanie Naim 3† , George Sharbeen 3 , Nelson Russia 3 , Julia Lee 3 , Maria Kavallaris 1,2 , David Goldstein 3 and Phoebe A. Phillips 3* 1

2 3

Tumour Biology and Targeting Program, Lowy Cancer Research Centre, Children’s Cancer Institute Australia, University of New South Wales, Sydney, NSW, Australia Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia

Edited by: Atsushi Masamune, Tohoku University Graduate School of Medicine, Japan Reviewed by: Kyoko Shimizu, Tokyo Women’s Medical University, Japan Shin Hamada, Tohoku University Graduate School of Medicine, Japan *Correspondence: Phoebe A. Phillips, Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, High St., Randwick, Sydney, NSW 2052, Australia e-mail: [email protected]

Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistance is enhanced. This review will discuss how PSCs contribute to chemoresistance in pancreatic cancer. Keywords: pancreatic cancer, chemoresistance, pancreatic stellate cells, stroma, fibrosis, hypoxia

† These authors have contributed equally to this work.

INTRODUCTION Pancreatic cancer is a highly aggressive malignancy with a notoriously dismal prognosis. Contributing to ∼227,000 annual deaths worldwide, this insidious disease is the fourth leading cause of cancer-related death in developed countries (Raimondi et al., 2009; Hidalgo, 2010; Vincent et al., 2011). Remarkably, 80–85% of patients present with unresectable and incurable tumors, putting the median survival period at