Advanced

Spontaneous lung and lymph node metastasis in transgenic breast cancer is independent of the urokinase receptor uPAR

Almholt, Kasper; Laerum, Ole Didrik; Nielsen, Boye Schnack; Lund, Ida Katrine; Lund, Leif Roge; Romer, John and Jögi, Annika LU (2015) In Clinical and Experimental Metastasis 32(6). p.543-554
Abstract
Urokinase-type plasminogen activator (uPA) is an extracellular protease that plays a pivotal role in tumor progression. uPA activity is spatially restricted by its anchorage to high-affinity uPA receptors (uPAR) at the cell surface. High tumor tissue expression of uPA and uPAR is associated with poor prognosis in lung, breast, and colon cancer patients in clinical studies. Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination. To investigate the role of uPAR in cancer progression, we analyze the effect of uPAR deficiency in the same cancer model. uPAR is predominantly expressed in stromal cells in the mouse... (More)
Urokinase-type plasminogen activator (uPA) is an extracellular protease that plays a pivotal role in tumor progression. uPA activity is spatially restricted by its anchorage to high-affinity uPA receptors (uPAR) at the cell surface. High tumor tissue expression of uPA and uPAR is associated with poor prognosis in lung, breast, and colon cancer patients in clinical studies. Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination. To investigate the role of uPAR in cancer progression, we analyze the effect of uPAR deficiency in the same cancer model. uPAR is predominantly expressed in stromal cells in the mouse primary tumors, similar to human breast cancer. In a cohort of MMTV-PyMT mice [uPAR-deficient (n = 31) or wild type controls (n = 33)], tumorigenesis, tumor growth, and tumor histopathology were not significantly affected by uPAR deficiency. Lung and lymph node metastases were also not significantly affected by uPAR deficiency, in contrast to the significant reduction seen in uPA-deficient mice. Taken together, our data show that the genetic absence of uPAR does not influence the outcome of the MMTV-PyMT cancer model. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Metastasis, uPAR, Antibody, Mouse model, Breast cancer
in
Clinical and Experimental Metastasis
volume
32
issue
6
pages
543 - 554
publisher
Springer
external identifiers
  • wos:000358249700003
  • scopus:84937966777
ISSN
1573-7276
DOI
10.1007/s10585-015-9726-1
language
English
LU publication?
yes
id
4be13970-a5da-4213-8200-83fd63b2242c (old id 7773668)
date added to LUP
2015-09-01 16:09:42
date last changed
2017-07-30 03:05:20
@article{4be13970-a5da-4213-8200-83fd63b2242c,
  abstract     = {Urokinase-type plasminogen activator (uPA) is an extracellular protease that plays a pivotal role in tumor progression. uPA activity is spatially restricted by its anchorage to high-affinity uPA receptors (uPAR) at the cell surface. High tumor tissue expression of uPA and uPAR is associated with poor prognosis in lung, breast, and colon cancer patients in clinical studies. Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination. To investigate the role of uPAR in cancer progression, we analyze the effect of uPAR deficiency in the same cancer model. uPAR is predominantly expressed in stromal cells in the mouse primary tumors, similar to human breast cancer. In a cohort of MMTV-PyMT mice [uPAR-deficient (n = 31) or wild type controls (n = 33)], tumorigenesis, tumor growth, and tumor histopathology were not significantly affected by uPAR deficiency. Lung and lymph node metastases were also not significantly affected by uPAR deficiency, in contrast to the significant reduction seen in uPA-deficient mice. Taken together, our data show that the genetic absence of uPAR does not influence the outcome of the MMTV-PyMT cancer model.},
  author       = {Almholt, Kasper and Laerum, Ole Didrik and Nielsen, Boye Schnack and Lund, Ida Katrine and Lund, Leif Roge and Romer, John and Jögi, Annika},
  issn         = {1573-7276},
  keyword      = {Metastasis,uPAR,Antibody,Mouse model,Breast cancer},
  language     = {eng},
  number       = {6},
  pages        = {543--554},
  publisher    = {Springer},
  series       = {Clinical and Experimental Metastasis},
  title        = {Spontaneous lung and lymph node metastasis in transgenic breast cancer is independent of the urokinase receptor uPAR},
  url          = {http://dx.doi.org/10.1007/s10585-015-9726-1},
  volume       = {32},
  year         = {2015},
}