Transformation potential of bone marrow stromal cells into undifferentiated high-grade pleomorphic sarcoma.
OBJECTIVE
Bone marrow adherent cells contain conventional bone marrow stromal cells and mesenchymal stem cells and these cells constitute the hematopoietic microenvironment. Mesenchymal stem cells have the capacity to give rise to multiple mesenchymal lineage cells and even ectodermal lineage cells. In the present study, we investigated what types of tumor cells are inducible from BM adherent cells by chemical carcinogens.


METHODS
Bone marrow cells from neonatal C3H/HeN mice were collected within 24 h after birth and then cultured. Four days later, bone marrow adherent cells were obtained and the cells were treated with 3-methylcholanthrene.


RESULTS
By this treatment, some transformed clones consisting of large spindle cells were obtained. The transformed cells were highly positive for CD44 and were positive for Sca-1, CD49d and CD106, whereas the cells were negative for hematolymphoid markers. The cell clones had the ability to support hematopoiesis in vitro. These results indicate that the transformed cell lines have the characteristics of BM stromal cells/mesenchymal stem cells. Moreover, during culture of the transformed cells, spontaneous bone nodule formation was observed. When the transformed cells were inoculated into immunodeficient mice subcutaneously, the neoplasms grew in the subcutaneous tissue of the mice. Microscopically and ultrastructurally, the neoplasms showed the typical morphology of undifferentiated high-grade pleomorphic sarcoma (UHGPS). Bone-related genes have been found to be expressed in both transformed cells and UHGPSs.


CONCLUSIONS
The present study suggests that UHGPSs are derived from BM stromal cells, probably mesenchymal stem cells.
Li
Qing
Q
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Hisha
Hiroko
H
Takaki
Takashi
T
Adachi
Yasushi
Y
Li
Ming
M
Song
Changye
C
Feng
Wei
W
Okazaki
Satoshi
S
Mizokami
Tomomi
T
Kato
Junko
J
Inaba
Muneo
M
Hosaka
Naoki
N
Maki
Masahiko
M
Ikehara
Susumu
S
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D019046:Bone Marrow Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008853:Microscopy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure