Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: Real-time PCR quantitation

Tester, Angus M, Sharp Julie, A, Dhanesuan, Nirada, Waltham, Mark and Thompson, Erik W 2002, Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: Real-time PCR quantitation, Clinical and Experimental Metastasis, vol. 19, no. 5, pp. 377-383.

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Title Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: Real-time PCR quantitation
Author(s) Tester, Angus M
Sharp Julie, A
Dhanesuan, Nirada
Waltham, Mark
Thompson, Erik W
Journal name Clinical and Experimental Metastasis
Volume number 19
Issue number 5
Start page 377
End page 383
Total pages 7
Publisher Springer Netherlands
Place of publication Amsterdam, Netherlands
Publication date 2002
ISSN 0262-0898
Keyword(s) Bone metastasis
Human breast cancer
Quantitative real-time PCR
Summary Orthotopic or intracardiac injection of human breast cancer cell lines into immunocompromised mice allows study of the molecular basis of breast cancer metastasis. We have established a quantitative real-time PCR approach to analyze metastatic spread of human breast cancer cells inoculated into nude mice via these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged with a bacterial β-galactosidase (Lac-Z) retroviral vector, enabling their detection by TaqMan® real-time PCR. PCR detection was linear, specific, more sensitive than conventional PCR, and could be used to directly quantitate metastatic burden in bone and soft organs. Attesting to the sensitivity and specificity of the PCR detection strategy, as few as several hundred metastatic MDA-MB-231 cells were detectable in 100 μm segments of paraffin-embedded lung tissue, and only in samples adjacent to sections that scored positive by histological detection. Moreover, the measured real-time PCR metastatic burden in the bone environment (mouse hind-limbs, n=48) displayed a high correlation to the degree of osteolytic damage observed by high resolution X-ray analysis (r 2=0.972). Such a direct linear relationship to tumor burden and bone damage substantiates the so-called `vicious cycle' hypothesis in which metastatic tumor cells promote the release of factors from the bone which continue to stimulate the tumor cells. The technique provides a useful tool for molecular and cellular analysis of human breast cancer metastasis to bone and soft organs, can easily be extended to other cell/marker/organ systems, and should also find application in preclinical assessment of anti-metastatic modalities.
Language eng
Field of Research 111201 Cancer Cell Biology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2002, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30061495

Document type: Journal Article
Collection: School of Medicine
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