Abstract
Background
The development of tumor micrometastases as an early event in the distribution of tumor cells to target organs, especially bone marrow, has been difficult to analyze due to a lack of suitably sensitive markers. The inability to discriminate small numbers of tumor cells from normal tissue cell populations has interfered with marker development.
Methods
To overcome this problem, human prostate cancer cell lines (PC-3) were labeled with bromodeoxyuridine (BrdU) and subsequently injected into athymic nude mice using the tail veins with or without compression of vena cava.
Results
Using a direct immunoperoxidase method with anti-BrdU monoclonal antibody, the BrdU-labeled tumor cells in the bone marrow stained intensely, while neighboring normal bone marrow cells were not stained. Staining of BrdU-labeled tumor cells is specific and extremely sensitive in detecting tumor cells in metastatic bone marrow.
Conclusions
These findings demonstrate the effectiveness and sensitivity of BrdU labeling as a maker in experimental studies for early metastatic events and that BrdU labeling provides a tool in virtually any tumor system for examining the distribution of tumor cells in target organs and their relationship to host organ microenvironments.
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References
Fidler IJ. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with1251-5-lodo-2′-deoxyuridine. J Natl Cancer Inst 1970;45:773–782.
Gratzner HG. Monoclonal antibody to 5-bromo-and 5-iododeoxyuridine: a new reagent for detection of DNA. Science 1982;218:474–475.
Nemoto R, Uchida K, Hattori K, Shimazui T, Koiso K, Harada M. S phase fraction of human prostate adenocarcinoma studied with in vivo bromodeoxyuridine labeling. Cancer 1990;66:509–514.
Nemoto R. New bone formation and cancer implants; relationship to tumor proliferative activity. Br J Cancer 1991;63:348–350.
Hu F, Wang RY, Hsu TC. Clonal origin of metastasis in B16 murin melanoma: a cytogenetic study. J Natl Cancer Inst 1987;78:155–163.
Schlimok G, Funke I, Holzmann G, Gottlinger G, Schmidt G, Hauser H, Swierkot S, Warnecke HH, Schneider B, Koprowski H, Reuthmuller G. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci USA 1987;84:8672–8676.
Lin WC, Pretlow TP, Oretlow II TG, Culp LA. Development of micrometastases: earliest events detected with bacterial lacZ gene tagged tumor cells. J Natl Cancer Inst 1990;82:1497–1503.
Nishijima Y, Koiso K, Nemoto R. The role of the vertebral veins in the dissemination of prostate carcinoma. Jpn J Urol 1995;86:927–932.
Batson OV. The function of the vertebral veins and their role in the spread of metastasis. Surg 1940;112:138–149.
Arguello F, Baggs RB, Frantz CN. A murine model of experimental metastasis to bone and bone marrow. Cancer Res 1988;48:6876–6881.
Nishijima Y, Koiso K, Nemoto R. Development of spinal metastasis by MBT-2 tumor in mice. Jpn J Urol 1994;85:1636–1642.
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Nishijima, Y., Nemoto, R. & Harada, M. New method to evaluate the distribution of metastatic tumor cells in bone marrow with bromodeoxyuridine labeling. Int J Clin Oncol 1, 131–134 (1996). https://doi.org/10.1007/BF02348377
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DOI: https://doi.org/10.1007/BF02348377