Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms

Heuijoon Park; Sonali Lad; Kelsey Boland; Kelly Johnson; Nyssa Readio; Guangchun Jin; Samuel Asfaha; Kelly S. Patterson; Ashok Singh; Xiangdong Yang; Douglas Londono; Anupama Singh; Carol Trempus; Derek Gordon; Timothy C. Wang; Rebecca J. Morris

doi:10.1038/s41467-018-07688-8

Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms

Heuijoon Park, Sonali Lad, Kelsey Boland, Kelly Johnson, Nyssa Readio, Guangchun Jin, Samuel Asfaha, Kelly S. Patterson, Ashok Singh, Xiangdong Yang, Douglas Londono, Anupama Singh, Carol Trempus, Derek Gordon, Timothy C. Wang, Rebecca J. Morris

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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.

Original language	English (US)
Article number	5293
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07688-8
State	Published - Dec 1 2018

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Publisher Copyright:
© 2018, The Author(s).

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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Park, H., Lad, S., Boland, K., Johnson, K., Readio, N., Jin, G., Asfaha, S., Patterson, K. S., Singh, A., Yang, X., Londono, D., Singh, A., Trempus, C., Gordon, D., Wang, T. C., & Morris, R. J. (2018). Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms. Nature Communications, 9(1), Article 5293. https://doi.org/10.1038/s41467-018-07688-8

Park, H, Lad, S, Boland, K, Johnson, K, Readio, N, Jin, G, Asfaha, S, Patterson, KS, Singh, A, Yang, X, Londono, D, Singh, A, Trempus, C, Gordon, D, Wang, TC & Morris, RJ 2018, 'Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms', Nature Communications, vol. 9, no. 1, 5293. https://doi.org/10.1038/s41467-018-07688-8

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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.",

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Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms

Abstract

Bibliographical note

PubMed: MeSH publication types

UN SDGs

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