Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages12
Published Date:Mar 2016
Source:Neoplasia. 2016; 18(3):142-151.
Pubmed Central ID:PMC4796803
Funding:DP2004403/DP/NCCDPHP CDC HHS/United States
1-R01-CA163345-01/CA/NCI NIH HHS/United States
R01 CA151588/CA/NCI NIH HHS/United States
1R01CA151588-01/CA/NCI NIH HHS/United States
T32 GM007863/GM/NIGMS NIH HHS/United States
T32 DK094775/DK/NIDDK NIH HHS/United States
T32 GM007315/GM/NIGMS NIH HHS/United States
R01 CA163345/CA/NCI NIH HHS/United States
Description:Pancreatic cancer is characterized by an extensive desmoplastic stroma, the functional relevance of which is poorly understood. Activated fibroblasts are a prevalent component of the stroma, and traditionally, these cells have been considered as a homogenous population derived from pancreatic stellate cells. In this study, we highlight a previously unappreciated heterogeneity of the fibroblast population within the stroma. In particular, a subset of stromal fibroblasts has characteristics of mesenchymal stem cells (MSCs). MSCs are present in the normal pancreas as well as in the carcinomatous pancreas (CA-MSCs). Here, we determine that CA-MSCs have increased tumor-promoting function compared with MSCs in normal pancreas. This ability to promote tumor growth is associated with CA-MSCs’ unique ability to promote alternative macrophage polarization. Thus, our study identifies a previously uncharacterized cell population within the stroma and sheds light on tumor-promoting interactions between different components of the stroma.
Targeting the stroma is emerging as a new paradigm in pancreatic cancer; however, efforts to that effect are hampered by our limited understanding of the nature and function of stromal components. Here, we uncover previously unappreciated heterogeneity within the stroma and identify interactions among stromal components that promote tumor growth and could be targeted therapeutically.
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