Desmoplasia in pancreatic ductal adenocarcinoma: insight into pathological function and therapeutic potential
Andrew Cannon1, Christopher Thompson1, Bradley R. Hall1,2 Maneesh Jain1,3, Sushil Kumar1 and Surinder K. Batra1,3
1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
2 Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
3 Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Correspondence:
Surinder K. Batra, email:
Correspondence:
Sushil Kumar, email:
Keywords: pancreatic ductal adenocarcinoma; desmoplasia; cancer-associated fibroblast; extracellular matrix; SHH
Received: March 27, 2018 Accepted: May 15, 2018 Published: May 21, 2018
Abstract
Extensive desmoplasia is a prominent feature of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Initially, studies demonstrated that desmoplasia promotes proliferation, invasion and chemoresistance in PDAC cells. While these findings suggested the therapeutic potential of targeting desmoplasia in PDAC, more recent studies utilizing genetically-engineered mouse models of PDAC, which lack key components of desmoplasia, demonstrated accelerated progression of PDAC. This contrast calls into question the paradigm that desmoplasia unilaterally promotes PDAC progression and the premise of desmoplasia-targeted therapy. This review briefly examines the major reports of the tumor-promoting and -restraining roles of desmoplasia in PDAC with commentary on the gaps in our current understanding of desmoplasia in PDAC. Additionally, we discuss the studies demonstrating the heterogeneous and multifaceted nature of desmoplasia in PDAC and advocate for future areas of research to thoroughly address the various facets of desmoplasia in PDAC, reconcile seemingly contradictory reports of the role of desmoplasia in PDAC progression, and discover aspects of desmoplasia that are therapeutically actionable.
