Benign mesenchymal stromal cells in human sarcomas.
OBJECTIVE
Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens.


METHODS
We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice.


RESULTS
We show that a dedifferentiated liposarcoma cell line DDLS8817 posesses fat, bone, and cartilage trilineage differentiation potential characteristic of MSCs. Primary sarcoma cultures have the morphology, surface immunophenotype, and differentiation potential characteristic of MSCs. Surprisingly, many of these cultures are benign, as they do not form tumors in mice and lack sarcoma-defining genetic lesions. Consistent with the recently proposed pericyte origin of MSCs in normal human tissues, sarcoma-derived benign MSCs (SDBMSCs) express markers of pericytes and cooperate with endothelial cells in tube formation assays. In human sarcoma specimens, a subset of CD146-positive microvascular pericytes expresses CD105, an MSC marker, whereas malignant cells largely do not. In an in vitro coculture model, SDBMSCs as well as normal human pericytes markedly stimulate the growth of sarcoma cell lines.


CONCLUSIONS
SDBMSCs/pericytes represent a previously undescribed stromal cell type in sarcoma that may contribute to tumor formation.
Departments of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. Alexmorozov1@gmail.com
Alexei
A
Morozov
Robert J
RJ
Downey
John
J
Healey
Andre L
AL
Moreira
Emil
E
Lou
Anna
A
Franceschino
Yildirim
Y
Dogan
Roland
R
Leung
Mark
M
Edgar
Michael
M
LaQuaglia
Robert G
RG
Maki
Malcolm A S
MA
Moore
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D012509:Sarcoma / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology* / Q000502:physiology*; D014183:Transplantation, Heterologous
C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit