title: Human Barrett's adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant.
abstract: This study characterizes the contribution of bone marrow-derived cells (BMDCs) to Barrett's adenocarcinoma of the esophagus using a mouse surgical model of disease and human specimens. Transplantation of bone marrow expressing beta galactosidase into a wild-type mouse, followed by surgical esophagojejunostomy, allowed tracking of BMDCs into the surgical anastomosis and resulting Barrett's metaplasia. Human tissue from a male patient who had been transplanted with female bone marrow and later developed esophageal adenocarcinoma allowed us to tract donor-derived cells into the tumor. Using a combination of antibodies directed against beta-galactosidase (animal studies) and X/Y fluorescent in situ hybridization (FISH) (human studies), combined with specific lineage staining directed against epithelial, fibroblast, endothelial, and leukocyte markers, we show that bone marrow cells contribute to both the epithelial and stromal component of esophageal adenocarcinoma. These findings demonstrate that BMDCs can generate cancer-associated fibroblasts as well as contribute directly to epithelial cells in cancer of the esophagus.
authors.affiliation: Department of Pathology, UMass Memorial Health Care, Worcester, MA, USA.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Hutchinson
authors.forename: Bjorn
authors.initials: B
authors.lastname: Stenstrom
authors.forename: Duan
authors.initials: D
authors.lastname: Chen
authors.forename: Bilal
authors.initials: B
authors.lastname: Piperdi
authors.forename: Sara
authors.initials: S
authors.lastname: Levey
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyle
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: JeanMarie
authors.initials: J
authors.lastname: Houghton
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000818:Animals; D001471:Barrett Esophagus / Q000473:pathology* / Q000601:surgery; D001854:Bone Marrow Cells / Q000473:pathology*; D004195:Disease Models, Animal; D004727:Endothelium / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008679:Metaplasia; D051379:Mice; D008875:Middle Aged; D058628:Myofibroblasts / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous