JeanMarie Houghton,^1* Calin Stoicov,¹ Sachiyo Nomura,^2,3 Arlin B. Rogers,⁴ Jane Carlson,¹ Hanchen Li,¹ Xun Cai,¹ James G. Fox,⁴ James R. Goldenring,^2,5 Timothy C. Wang^1*

Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow–derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.

¹ Department of Medicine and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

² Epithelial Biology Program, Department of Surgery and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

³ Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.

⁴ Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

⁵ The Veterans Administration Medical Center, Nashville, TN 37232, USA.

Present address: Department of Medicine and Cancer Center, Columbia College of Physicians and Surgeons, New York, NY 10032, USA.

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