title: Bone marrow contributes to epithelial cancers in mice and humans as developmental mimicry.
abstract: Bone marrow cells have the capacity to contribute to distant organs. We show that marrow also contributes to epithelial neoplasias of the small bowel, colon, and lung, but not the skin. In particular, epithelial neoplasias found in patients after hematopoietic cell transplantations demonstrate that human marrow incorporates into neoplasias by adopting the phenotype of the surrounding neoplastic environment. To more rigorously evaluate marrow contribution to epithelial cancer, we employed mouse models of intestinal and lung neoplasias, which revealed specifically that the hematopoietic stem cell and its progeny incorporate within cancer. Furthermore, this marrow involvement in epithelial cancer does not appear to occur by induction of stable fusion. Whereas previous claims have been made that marrow can serve as a direct source of epithelial neoplasia, our results indicate a more cautionary note, that marrow contributes to cancer as a means of developmental mimicry. Disclosure of Potential Conflicts of Interest is found at the end of this article.
authors.affiliation: Program in Stem Cell Biology and Regenerative Medicine, University of Florida, ARB R4-216B, Gainesville, FL 32610-0277, USA. c@ufl.edu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.forename: Dongtao
authors.initials: D
authors.lastname: Fu
authors.forename: Deniz
authors.initials: D
authors.lastname: Ucar
authors.forename: Sean
authors.initials: S
authors.lastname: Lee
authors.forename: Steven M
authors.initials: SM
authors.lastname: Guthrie
authors.forename: Jean
authors.initials: J
authors.lastname: Lonergan
authors.forename: Witold
authors.initials: W
authors.lastname: Rybka
authors.forename: Diane S
authors.initials: DS
authors.lastname: Krause
authors.forename: Edward W
authors.initials: EW
authors.lastname: Scott
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000473:pathology; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000473:pathology; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D018716:Molecular Mimicry; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000473:pathology