Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein.
BACKGROUND
An in vivo spontaneous metastatic model using androgen-sensitive prostate cancer cells is needed to the better understanding of prostate cancer progression. Orthotopically inoculated LNCaP cells to SCID mice manifests metastases, but it takes no less than 12 weeks to detect them by conventional methods.


METHODS
The green fluorescent protein (GFP) gene was introduced into LNCaP cells by conventional lipofection technique. Biological characteristics of a subline (LNCaP-GFP) that expressed GFP at high level were compared to those of the parental cells. LNCaP-GFP cells were orthotopically inoculated to the SCID mouse, and metastases to distant organs were chronologically examined under fluorescence microscopy.


RESULTS
There was no difference in growth rates and androgen-responsiveness in vitro between LNCaP-GFP and LNCaP cells. LNCaP-GFP cells inoculated to SCID mice produced prostate specific antigen. Histopathological examination at 12 weeks after inoculation of LNCaP-GFP revealed that metastases were identified as the inoculation of LNCaP cells. Colonies consisting of a few LNCaP-GFP cells, however, were detected in the lung under fluorescence microscopy as early as 4 weeks after inoculation.


CONCLUSIONS
Orthotopic inoculation of LNCaP-GFP to SCID mice may provide a useful tool to investigate the molecular mechanism of progression, in particular the early stage of metastasis, of androgen-sensitive prostate cancer cells.
Maeda
H
H
Department of Urology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Segawa
T
T
Kamoto
T
T
Yoshida
H
H
Kakizuka
A
A
Ogawa
O
O
Kakehi
Y
Y
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000502:physiology; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000175:diagnosis / Q000235:genetics / Q000556:secondary*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology*
D000728:Androgens; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins