@article{ee11093b0f8b4548bf93bdccb0c7e98d,
title = "Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture",
abstract = "Objective Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the United States. Improved characterized models of PDAC are needed for drug screening. Methods We grew 4 established pancreatic cancer cell lines in hanging drop cultures to produce spheroids. We also grew organoids from explanted xenografted PDAC and surgically resected primary PDAC. We performed transmission and scanning electron microscopy and compared findings with those of the normal pancreatic duct. We also performed single-cell cloning to determine the potential options for differentiation. Results Spheroids contained tight junctions and desmosomes but lacked zymogen granules, as expected. The former features were present in normal pancreatic duct but absent from PDAC cell lines grown in standard 2-dimensional culture. Spheroids functionally excluded macromolecules in whole mounts. Cells on the surface of PDAC spheroids were carpeted by microvilli except for rare cells with prominent stereocilia. Carpets of microvilli were also seen in low passage organoids produced from xenografts and surgically resected human PDAC, in addition to normal human pancreatic duct. We performed single-cell cloning and resulting spheroids produced both cell phenotypes at the same approximate ratios as those from bulk cultures. Conclusions Pancreatic cancer spheroids/organoids are capable of biphenotypic differentiation.",
keywords = "PDAC, biphenotypic differentiation, microvilli, organoids, spheroids, stereocilia",
author = "Yoshihisa Matsushita and Barbara Smith and Michael Delannoy and Trujillo, {Maria A.} and Peter Chianchiano and Ross McMillan and Hirohiko Kamiyama and Hong Liang and Thompson, {Elizabeth D.} and Hruban, {Ralph H.} and William Matsui and Wood, {Laura D.} and Roberts, {Nicholas J.} and Eshleman, {James R.}",
note = "Funding Information: From the *Department of Pathology, Johns Hopkins University School of Medicine, The Sol Goldman Pancreatic Cancer Research Center; †Department of Cell Biology, Johns Hopkins University School of Medicine; ‡Department of Oncology, Johns Hopkins University School of Medicine; and §Department of Oncology, Johns Hopkins University School of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Baltimore, MD. Received for publication February 12, 2019; accepted July 31, 2019. Address correspondence to: James R. Eshleman, MD, PhD, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, CRB II, Rm 344, 1550 Orleans St, Baltimore, MD 21231 (e‐mail: jeshlem@jhmi.edu). This work was supported in part by the Sol Goldman Pancreatic Cancer Research Center, the Stringer Foundation, Michael Rolfe Pancreatic Cancer Foundation, Mary Lou Wootton Pancreatic Cancer Research Fund, the Gerald O. Mann Charitable Foundation (Harriet and Allan Wulfstat Trustees), the Joseph C. Monastra Foundation, Susan Wojcicki and Dennis Troper, in addition to grants from the National Institutes of Health Grant P50 CA62924, the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH grants P30CA006973, RO1 CA190889, and UL1TR001079), and the Shared Instrument Grant (S10RR026824). The authors declare no conflict of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal{\textquoteright}s Web site (www.pancreasjournal.com). Copyright {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MPA.0000000000001390 Publisher Copyright: {\textcopyright} Wolters Kluwer Health, Inc. All rights reserved.",
year = "2019",
month = oct,
day = "1",
doi = "10.1097/MPA.0000000000001390",
language = "English (US)",
volume = "48",
pages = "1225--1231",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "9",
}