Keratin 13 Is Enriched in Prostate Tubule-Initiating ... - Semantic Scholar

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Oct 6, 2016 - Veterans Affairs Healthcare System, Los Angeles, California, United States of America, 8 Department of. Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, ..... Western blot analysis.
RESEARCH ARTICLE

Keratin 13 Is Enriched in Prostate TubuleInitiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone a11111

OPEN ACCESS Citation: Liu S, Cadaneanu RM, Zhang B, Huo L, Lai K, Li X, et al. (2016) Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone. PLoS ONE 11(10): e0163232. doi:10.1371/ journal.pone.0163232

Sandy Liu1☯, Radu M. Cadaneanu2☯, Baohui Zhang2, Lihong Huo2, Kevin Lai2, Xinmin Li3, Colette Galet2, Tristan R. Grogan4, David Elashoff4, Stephen J. Freedland5, Matthew Rettig2,6, William J. Aronson2,6,7, Beatrice S. Knudsen8, Michael S. Lewis9, Isla P. Garraway2,6,7* 1 Department of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America, 2 Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America, 3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America, 4 Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America, 5 Urologic Section, Department of Surgery, Durham VA Medical Center, Durham, North Carolina, United States of America, 6 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, United States of America, 7 Urology Section, Department of Surgery, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, United States of America, 8 Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America, 9 Department of Pathology, Greater Los Angeles Veterans Affairs Health System, Los Angeles, California, United States of America ☯ These authors contributed equally to this work. * [email protected]

Editor: Rajeev Samant, University of Alabama at Birmingham, UNITED STATES Received: June 23, 2016

Abstract

Accepted: September 6, 2016 Published: October 6, 2016

Background

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated.

Data Availability Statement: All relevant data are within the paper and the Gene Expression Omnibus public archive. Gene expression data is available at the following URL: http://www.ncbi.nlm.nih.gov/ geo/query/acc.cgi?acc=GSE86904. Funding: This work was supported by Jean Perkins Foundation (IG); Prostate Cancer Foundation (PCF) Creativity Award (BK); Movember/PCF GAP1 Unique TMAs Project (IG, ML, and BK); Stephen Spielberg Team Science Award (BK); DOD PC131996 (IG, ML, and BK); DOD PC130244 (IG and ML); NIH/NCI P01 CA098912-09 (IG and BK);

Results Gene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p