Bone marrow contributes to epithelial cancers in mice and humans as developmental mimicry.
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.
Cogle
Christopher R
CR
Program in Stem Cell Biology and Regenerative Medicine, University of Florida, ARB R4-216B, Gainesville, FL 32610-0277, USA. c@ufl.edu
Theise
Neil D
ND
Fu
Dongtao
D
Ucar
Deniz
D
Lee
Sean
S
Guthrie
Steven M
SM
Lonergan
Jean
J
Rybka
Witold
W
Krause
Diane S
DS
Scott
Edward W
EW
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