title: Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Esha
authors.initials: E
authors.lastname: Mathew
authors.affiliation: Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brannon
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: AnnaChiara
authors.initials: A
authors.lastname: Del Vecchio
authors.affiliation: Program in Pathology, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Paloma E
authors.initials: PE
authors.lastname: Garcia
authors.affiliation: Program in Cancer Biology, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Morgan K
authors.initials: MK
authors.lastname: Penny
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Kane
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Alekya
authors.initials: A
authors.lastname: Vinta
authors.affiliation: Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Buckanovich
authors.affiliation: Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, 48109; Department of Surgery, University of Michigan, Ann Arbor, MI, 48109; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109. Electronic address: marinapa@umich.edu.
authors.forename: Marina Pasca
authors.initials: MP
authors.lastname: di Magliano
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D006801:Humans; D008264:Macrophages; D059630:Mesenchymal Stem Cells; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D059016:Tumor Microenvironment / Q000235:genetics*