Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers.
Tumor development is a complex and dynamic process that involves malignant, vascular, and stromal cells. Endosialin is a tumor endothelial marker (TEM) present in the microvasculature and stroma of human tumors. Cancer-associated fibroblasts (CAF) have been implicated in promoting tumor development and have been associated with mesenchymal stem cells (MSC). Since stem/progenitor cells recruited either from bone marrow or residing in nearby tissues can contribute to pathological processes we investigated endosialin in MSC using a novel monoclonal antibody. Endosialin is highly expressed by CAF and human bone marrow-derived MSC. MSC can form networks in a tube formation assay that is inhibited by an anti-endosialin antibody. Immunohistochemistry for human endosialin in xenograft tumors following co-injection of MSC and cancer cells identified MSC in tumor stroma. MSC are a potential target for anticancer therapeutic intervention and endosialin expression offers a new tool for the identification of MSC. Endosialin expression by both CAF and MSC further implies the potential contribution of MSC to tumor stroma via differentiation into tumor stromal fibroblasts.
Bagley
Rebecca G
RG
Genzyme Corporation, Framingham, MA 01701-9322, USA. rebecca.bagley@genzyme.com
Weber
William
W
Rouleau
Cecile
C
Yao
Min
M
Honma
Nakayuki
N
Kataoka
Shiro
S
Ishida
Isao
I
Roberts
Bruce L
BL
Teicher
Beverly A
BA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C078203:CD248 protein, human