Abstract

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.

Details

Title
Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms
Author
Park, Heuijoon 1 ; Lad, Sonali 2 ; Boland, Kelsey 2 ; Johnson, Kelly 2 ; Readio, Nyssa 2 ; Jin, Guangchun 3 ; Asfaha, Samuel 3 ; Patterson, Kelly S 3 ; Singh, Ashok 2 ; Yang, Xiangdong 3 ; Londono, Douglas 4 ; Singh, Anupama 2 ; Trempus, Carol 5 ; Gordon, Derek 4 ; Wang, Timothy C 3 ; Morris, Rebecca J 6 

 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Department of Dermatology, Columbia University, New York, NY, USA; Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, NY, USA; The Hormel Institute, University of Minnesota, Austin, MN, USA 
 The Hormel Institute, University of Minnesota, Austin, MN, USA 
 Division of Digestive and Liver Diseases, Department of Medicine and Irving Cancer Center, Columbia University, New York, NY, USA 
 Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA 
 Matrix Biology Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA 
 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Department of Dermatology, Columbia University, New York, NY, USA; The Hormel Institute, University of Minnesota, Austin, MN, USA 
Pages
1-15
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2155915267
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.