@article{2fd9d921b539498f8ff0009be6ed8360,
title = "Paracrine Secretion of Transforming Growth Factor β by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues",
abstract = "Objective We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. Methods We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. Results A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor β (TGF-β) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-β to induce ADM in human acinar cells. In addition, we found that TGF-β cannot induce ADM of murine acinar cells. Conclusions Ductal cells are the major source of TGF-β that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.",
keywords = "TGF-β, acinar cells, human, metaplasia",
author = "Naoki Akanuma and Jun Liu and Liou, {Geou Yarh} and Xue Yin and Bejar, {Kaitlyn R.} and Chengyang Liu and Sun, {Lu Zhe} and Peter Storz and Pei Wang",
note = "Funding Information: From the *Departments of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX; †Department of Cancer Biology, Mayo Clinic, Jacksonville, FL; and ‡Surgery Department, University of Pennsylvania School of Medicine, Philadelphia, PA. Received for publication December 8, 2016; accepted July 31, 2017. Address correspondence to: Pei Wang, PhD, Department of Cell Systems and Anatomy, HSC-MED 2.067V, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr. San Antonio, TX 78229 (e‐mail: wangp3@uthscsa.edu). This work was supported by the Cancer Prevention and Research Institute of Texas (to P.W.) and National Institutes of Health grant CA200572 (to P.S.). P.W. is a Cancer Prevention and Research Institute of Texas scholar. J.L. is supported by a training grant from the Cancer Prevention and Research Institute of Texas (RP140105). Data were generated in the Flow Cytometry Shared Resource Facility, which is supported by the University of Texas Health Science Center at San Antonio, NIH-NCI P30 CA054174-20 (Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio) and UL1 TR001120 (Clinical and Translational Science Awards grant). The authors declare no conflict of interest. Copyright {\textcopyright} 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MPA.0000000000000913 Publisher Copyright: Copyright {\textcopyright} 2017 Wolters Kluwer Health, Inc. All rights reserved.",
year = "2017",
month = oct,
day = "1",
doi = "10.1097/MPA.0000000000000913",
language = "English (US)",
volume = "46",
pages = "1202--1207",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "9",
}