Abstract 5202: Bone marrow-derived epithelial cells contribute to chronic skin inflammation and skin tumor formation in the mouse

Abstract

Abstract Although a stem cell origin for tumors was postulated nearly 200 years ago, a critical role of keratin-15 expressing hair follicle stem cells in skin tumorigenesis has only recently been established. In addition to tissue stem cells, bone marrow cells can play a reparative function in damaged organs and contribute to cancer development as recently demonstrated in a gastric cancer model of Helicobacter felis-induced chronic inflammation. We report here that bone marrow derived cells (BMDCs) are an exogenous source of epithelial cells in tumor development in the multistage skin carcinogenesis model following gender mismatched allogeneic bone marrow transplantation. First, clusters of BMDCs were detected in the epithelium of 37.78% papilloma samples with a genetic marker (EGFP) indicating their bone marrow donor origin. Second, clusters of keratin immunoreactive BMDCs were located primarily in the basal epithelium of the papillomas. Third, a subset of BMDCs in the basal epithelium was found to be highly proliferative as measured by incorporation of BrdU and expression of Ki67. Furthermore, a significant contribution of BMDCs was identified in 53.06% of ulcer-associated dysplastic skin samples by immunostaining and confirmed by presence of a Y chromosome. Moreover, an enhanced contribution of bone marrow-derived epithelial cells was observed in the dysplastic epidermis. Therefore, these results demonstrate that a subset of BMDCs participates as a new epithelial cell source in chronically damaged skin lesions including papillomas and ulcers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5202. doi:1538-7445.AM2012-5202