Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder

Chaffer, C.L., Dopheide, B., McCulloch, D.R., Lee, A.B., Moseley, J.M., Thompson, E.W., & Williams, E.D. (2005) Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder. Clinical and Experimental Metastasis, 22(2), pp. 115-125.

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Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.

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40 citations in Web of Science®
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ID Code: 71906
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):36
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 16086232
Additional URLs:
Keywords: Animal model, Bladder, Metastatic, MMP-9, MT1-MMP, Osteosclerotic, TIMP-2, Transitional cell carcinoma
DOI: 10.1007/s10585-005-5141-3
ISSN: 1573-7276
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 22 May 2014 00:53
Last Modified: 21 Jun 2017 11:01

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