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


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.

SUBMITTER: Park H 

PROVIDER: S-EPMC6294255 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Park Heuijoon H   Lad Sonali S   Boland Kelsey K   Johnson Kelly K   Readio Nyssa N   Jin Guangchun G   Asfaha Samuel S   Patterson Kelly S KS   Singh Ashok A   Yang Xiangdong X   Londono Douglas D   Singh Anupama A   Trempus Carol C   Gordon Derek D   Wang Timothy C TC   Morris Rebecca J RJ  

Nature communications 20181213 1


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) cul  ...[more]

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