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CANCER STEM CELLS

Bone Marrow Contributes to Epithelial Cancers in Mice and Humans as Developmental Mimicry

^aProgram in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, Florida, USA;
^bDepartments of Medicine and Pathology, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York, USA;
^cDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA;
^dSt. Francis Hospital, Indiana Blood and Marrow Transplantation, Indianapolis, Indiana, USA;
^eHershey Medical Center, Hershey, Pennsylvania, USA

Key Words. Bone marrow cells • Malignancy • Differentiation • Plasticity • Hematopoietic stem cell • Bone marrow transplantation

Correspondence: Christopher R. Cogle, M.D., University of Florida, 1600 SW Archer Road, ARB R4-216B, P.O. Box 100277, Gainesville, Florida 32610-0277, USA. Telephone: 352-392-3058; Fax: 352-392-8530; e-mail: c{at}ufl.edu

Received March 8, 2007; accepted for publication April 20, 2007.
First published online in STEM CELLS EXPRESS   May 3, 2007.



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.

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