Abstract
The serine protease urokinase-type plasminogen activator, uPA, when bound to its specific receptor, uPAR (CD87), plays a significant role in tumor cell invasion and metastasis. In breast cancer, enhanced uPA antigen in the primary tumor is correlated with poor prognosis of the patient. In an in vivo nude mouse model, we tested tumor growth and metastasis of human breast carcinoma cells that had been transfected with an expression plasmid encoding a soluble form of uPAR (suPAR). We explored, whether suPAR/uPA interaction reduces the binding of uPA to cell surface-associated uPAR, and, as a consequence, could suppress tumor growth and metastasis of the human breast cancer cell line MDA-MB-231 BAG. Overexpressed, secreted suPAR was shown to bind and thus scavenge the uPA secreted by the transfected lines suPAR3 and suPAR10. In vitro, an overexpression of suPAR did not alter the proliferation rate of the transfected tumor cells, nor did it affect the expression of uPA. Overexpression of suPAR led to a reduction in the plasminogen activation-related proteolytic activity of breast carcinoma cells. Primary tumor growth in the mammary fat pad of nude mice was followed up for 52 days. Overexpression of suPAR correlated with a reduction in tumor growth (from day 21, reaching 30% by day 34) as well as lung colonization (lung metastasis-positive mice in suPAR3: 4 of 17; suPAR10: 3 of 10; parental MDA-MB-231 BAG: 13 of 18). We conclude that suPAR overexpression leading to effective scavenge of uPA impairs proteolysis as well as the tumor growth and metastatic potential of breast carcinoma cells in vivo.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Krüger, A., Soeltl, R., Lutz, V. et al. Reduction of breast carcinoma tumor growth and lung colonization by overexpression of the soluble urokinase-type plasminogen activator receptor (CD87). Cancer Gene Ther 7, 292–299 (2000). https://doi.org/10.1038/sj.cgt.7700144
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cgt.7700144
Keywords
This article is cited by
-
Signatures of prostate-derived Ets factor (PDEF) in cancer
Tumor Biology (2016)
-
Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo
Breast Cancer Research and Treatment (2011)
-
Regulation of cell signalling by uPAR
Nature Reviews Molecular Cell Biology (2010)
-
Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator
Oncogene (2002)