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

Tester, A.M., Sharp, J.A., Dhanesuan, N., Waltham, M., & Thompson, E.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, 19(5), pp. 377-383.

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Abstract

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 (r2 = 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.

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10 citations in Scopus
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10 citations in Web of Science®

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ID Code: 71916
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):10
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 12198765
Additional URLs:
Keywords: Bone metastasis, Human breast cancer, Quantitative real-time PCR
DOI: 10.1023/A:1016381416463
ISSN: 1573-7276
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 21 May 2014 04:03
Last Modified: 21 May 2014 04:03

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