Gastric Cancer Originating from Bone Marrow-Derived Cells

TLDR

Epithelial cancers are generally thought to arise from transformed tissue stem cells, yet bone marrow–derived cells recruited to injured tissues may also serve as a malignant source. Chronic Helicobacter infection in mice induces bone marrow–derived cells to repopulate the stomach, progress through metaplasia and dysplasia, and ultimately form intraepithelial cancer, demonstrating that epithelial cancers can originate from marrow‑derived cells.

Abstract

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.