Involvement of bone marrow-derived stromal cells in gastrointestinal cancer development and metastasis.
BACKGROUND
The involvement of bone marrow (BM) in tumor-stroma reactions or tumor development has not been examined in a cancer allograft, which has otherwise been appropriate for assessing therapeutic modalities. We investigated the fate of BM-derived cells in colon cancer allografts and liver metastases in mice.


METHODS
C57BL/6 mice were irradiated and rescued by BM transplantation from green fluorescent protein (GFP)-transgenic mice. MC38 colon cancer cells were stably transfected with the pDsRed gene in order to identify tumor cells by fluorescence. These were inoculated into the mice to generate subcutaneous allografted tumors or liver metastases. The tumors were observed under confocal microscopy and fluorescent immunohistochemistry to determine the fate of tumor versus BM-derived cells.


RESULTS
GFP-positive (GFP(+)) cells were consistently identified as vimentin(+), alpha-smooth muscle actin (alphaSMA)(+), spindle-shaped stromal cells in both the subcutaneous tumors and the liver metastases. GFP(+) cells of leukocyte lineage also infiltrated the tumors. Neither GFP(+) CD31(+) endothelial cells nor GFP(+) DsRed(+) cells were detected in the tumor.


CONCLUSIONS
BM-derived cells frequently and consistently infiltrated the tumor allografts and metastases as interstitial cells and leukocytes. Cells derived from the fusion of BM cells and tumor cells were not observed. This model may be appropriate for the clarification of the effects of anticancer therapies and the study of BM-derived cells in tumor-host interactions.
Ishii
Shuji
S
Departments of Gastroenterology and Hepatology, Osaka University Graduate School of Medcine, Suita, Osaka, Japan.
Tsuji
Shingo
S
Tsujii
Masahiko
M
Kanazawa
Yoshiyuki
Y
Nishida
Tsutomu
T
Iijima
Hideki
H
Yasumaru
Masakazu
M
Irie
Takanobu
T
Yamamoto
Katsumi
K
Tsutsui
Shusaku
S
Eguchi
Hiroshi
H
Kawano
Sunao
S
Hayashi
Norio
N
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014916:Whole-Body Irradiation; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C485184:enhanced green fluorescent protein