Gastric cancer originating from bone marrow-derived cells.
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.
Houghton
Jeanmarie
J
Department of Medicine and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. jeanmarie.houghton@umassmed.edu
Stoicov
Calin
C
Nomura
Sachiyo
S
Rogers
Arlin B
AB
Carlson
Jane
J
Li
Hanchen
H
Cai
Xun
X
Fox
James G
JG
Goldenring
James R
JR
Wang
Timothy C
TC
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002278:Carcinoma in Situ / Q000473:pathology; D002454:Cell Differentiation; D002459:Cell Fusion; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology; D005756:Gastritis / Q000473:pathology*; D016481:Helicobacter Infections / Q000473:pathology*; D044922:Helicobacter felis; D007633:Keratins / Q000032:analysis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009077:Mucins / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D010295:Parietal Cells, Gastric / Q000502:physiology; D010455:Peptides / Q000032:analysis; D010641:Phenotype; D013234:Stem Cells / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D000071164:Trefoil Factor-2
D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2; D007633:Keratins