Topic Highlight
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2016; 22(9): 2678-2700
Published online Mar 7, 2016. doi: 10.3748/wjg.v22.i9.2678
Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells
Michael Friberg Bruun Nielsen, Michael Bau Mortensen, Sönke Detlefsen
Michael Friberg Bruun Nielsen, Sönke Detlefsen, Department of Pathology, Odense University Hospital, University of Southern Denmark, 5000 Odense, Denmark
Michael Bau Mortensen, Department of Surgery, HPB Section, Odense University Hospital, University of Southern Denmark, 5000 Odense, Denmark
Author contributions: Nielsen MFB and Detlefsen S drafted the manuscript; and Mortensen MB revised the manuscript.
Supported by University of Southern Denmark; and Odense University Hospital Research Fund.
Conflict-of-interest statement: The authors report no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sönke Detlefsen, MD, PhD, Clinical Associate Professor, Consultant Pathologist, Department of Pathology, Odense University Hospital, University of Southern Denmark, 5000 Odense, Denmark.
Telephone: +45-65414806 Fax: +45-65912943
Received: September 29, 2015
Peer-review started: September 29, 2015
First decision: November 13, 2015
Revised: December 19, 2015
Accepted: January 11, 2016
Article in press: January 11, 2016
Published online: March 7, 2016

Pancreatic cancer (PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts (CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and non-cellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a context-dependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.

Keywords: Pancreatic cancer, Desmoplastic stroma, Cancer-associated fibroblast, Inflammatory cells, Pancreatic stellate cell

Core tip: Pancreatic cancer (PC), the most aggressive type of common cancers, is characterized by a limited response to chemotherapeutics, which are often directed against the PC cells. One of the histological hallmarks of PC is the extensive desmoplastic stromal reaction that surrounds the PC cells. The PC stroma is not simply a bystander of the neoplastic process but plays an active part in disease progression and metastasis. The PC cells, cancer-associated fibroblasts, inflammatory cells, endothelial cells, and the extracellular matrix engage in a complex interplay, the modulation of which could hold potential for the future development of new PC therapies.