PMID- 30546048 OWN - NLM STAT- MEDLINE DCOM- 20190122 LR - 20231005 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Dec 13 TI - Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms. PG - 5293 LID - 10.1038/s41467-018-07688-8 [doi] LID - 5293 AB - We used allogeneic bone marrow transplantation (BMT) and a mouse multistage cutaneous carcinogenesis model to probe recruitment of bone marrow-derived epithelial cells (BMDECs) in skin tumors initiated with the carcinogen, dimethylbenz[a]anthracene (DMBA), and promoted with 12-O-tetradecanolyphorbol-13-acetate (TPA). BMDECs clustered in the lesional epithelium, expressed cytokeratins, proliferated, and stratified. We detected cytokeratin induction in plastic-adherent bone marrow cells (BMCs) cultured in the presence of filter-separated keratinocytes (KCs) and bone morphogenetic protein 5 (BMP5). Lineage-depleted BMCs migrated towards High Mobility Group Box 1 (HMGB1) protein and epidermal KCs in ex vivo invasion assays. Naive female mice receiving BMTs from DMBA-treated donors developed benign and malignant lesions after TPA promotion alone. We conclude that BMDECs contribute to the development of papillomas and dysplasia, demonstrating a systemic contribution to these lesions. Furthermore, carcinogen-exposed BMCs can initiate benign and malignant lesions upon tumor promotion. Ultimately, these findings may suggest targets for treatment of non-melanoma skin cancers. FAU - Park, Heuijoon AU - Park H AD - Department of Pathology and Cell Biology, Columbia University, New York, 10032, NY, USA. AD - Department of Dermatology, Columbia University, New York, 10032, NY, USA. AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Lad, Sonali AU - Lad S AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Boland, Kelsey AU - Boland K AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Johnson, Kelly AU - Johnson K AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Readio, Nyssa AU - Readio N AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Jin, Guangchun AU - Jin G AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. FAU - Asfaha, Samuel AU - Asfaha S AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. FAU - Patterson, Kelly S AU - Patterson KS AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. FAU - Singh, Ashok AU - Singh A AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Yang, Xiangdong AU - Yang X AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. FAU - Londono, Douglas AU - Londono D AD - Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, 08854-8082, NJ, USA. FAU - Singh, Anupama AU - Singh A AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. FAU - Trempus, Carol AU - Trempus C AD - Matrix Biology Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709, NC, USA. FAU - Gordon, Derek AU - Gordon D AD - Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, 08854-8082, NJ, USA. FAU - Wang, Timothy C AU - Wang TC AD - Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, 10032, NY, USA. FAU - Morris, Rebecca J AU - Morris RJ AD - Department of Pathology and Cell Biology, Columbia University, New York, 10032, NY, USA. rmorris@hi.umn.edu. AD - Department of Dermatology, Columbia University, New York, 10032, NY, USA. rmorris@hi.umn.edu. AD - The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA. rmorris@hi.umn.edu. LA - eng GR - R01 AR052713/AR/NIAMS NIH HHS/United States GR - R01 CA097957/CA/NCI NIH HHS/United States GR - R21 CA124942/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20181213 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Bmp5 protein, mouse) RN - 0 (Bone Morphogenetic Protein 5) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene) RN - 68238-35-7 (Keratins) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - 9,10-Dimethyl-1,2-benzanthracene/toxicity MH - Animals MH - Bone Marrow Cells/cytology/*pathology MH - Bone Marrow Transplantation MH - Bone Morphogenetic Protein 5/metabolism MH - Cell Movement MH - Cell Plasticity/physiology MH - Cell Transformation, Neoplastic/*chemically induced/*pathology MH - Coculture Techniques MH - Epithelial Cells/cytology/*pathology MH - Female MH - HMGB1 Protein/metabolism MH - Hair Follicle/cytology MH - Keratinocytes/pathology MH - Keratins/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neoplasm Invasiveness/pathology MH - Papilloma/pathology MH - Skin Neoplasms/*pathology MH - Stem Cells/cytology/pathology MH - Tetradecanoylphorbol Acetate/toxicity MH - Tumor Cells, Cultured PMC - PMC6294255 COIS- The authors declare no competing interests. EDAT- 2018/12/14 06:00 MHDA- 2019/01/23 06:00 PMCR- 2018/12/13 CRDT- 2018/12/15 06:00 PHST- 2014/03/17 00:00 [received] PHST- 2018/11/09 00:00 [accepted] PHST- 2018/12/15 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2019/01/23 06:00 [medline] PHST- 2018/12/13 00:00 [pmc-release] AID - 10.1038/s41467-018-07688-8 [pii] AID - 7688 [pii] AID - 10.1038/s41467-018-07688-8 [doi] PST - epublish SO - Nat Commun. 2018 Dec 13;9(1):5293. doi: 10.1038/s41467-018-07688-8.