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First published online May 3, 2007
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2007-0163v1
25/8/1881    most recent
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Submitted on March 8, 2007
Accepted on April 20, 2007

CANCER STEM CELLS

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

Christopher R. Cogle 1*, Neil D. Theise 2, DongTao Fu 1, Deniz Ucar 1, Sean Lee 3, Steven M. Guthrie 1, Jean Lonergan 4, Witold Rybka 5, Diane S. Krause 3, Edward W. Scott 1

1 Program in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, FL, USA
2 Departments of Medicine and Pathology, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY, USA
3 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA
4 St. Francis Hospital, Indiana Blood and Marrow Transplantation, Indiana, USA
5 Hershey Medical Center, Hershey, PA, USA

* To whom correspondence should be addressed. E-mail: c{at}ufl.edu.


  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.

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




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