Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice. / Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen; Nielsen, Boye Schnack; Danø, Keld; Nielsen, John Rømer; Johnsen, Morten.
I: International Journal of Cancer, Bind 113, Nr. 4, 2005, s. 525-32.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice
AU - Almholt, Kasper
AU - Lund, L.R.
AU - Rygaard, Jørgen
AU - Nielsen, Boye Schnack
AU - Danø, Keld
AU - Nielsen, John Rømer
AU - Johnsen, Morten
N1 - Keywords urokinase-type plasminogen activator • plasminogen • proteolysis • mouse model • breast cancer
PY - 2005
Y1 - 2005
N2 - A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume was reduced from 1.58 mm3 in wild-type controls to 0.21 mm3 in uPA-deficient mice (p = 0.023). Tumor cell dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild-type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without plasminogen display a severe pleiotropic phenotype. By comparison, spontaneous phenotypes are modest in uPA-deficient mice, probably because they still have active tPA. We show that metastasis is strongly and selectively decreased in uPA-deficient mice, suggesting that uPA-directed antimetastatic therapy would be efficacious and have limited side effects. © 2004 Wiley-Liss, Inc.
AB - A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume was reduced from 1.58 mm3 in wild-type controls to 0.21 mm3 in uPA-deficient mice (p = 0.023). Tumor cell dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild-type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without plasminogen display a severe pleiotropic phenotype. By comparison, spontaneous phenotypes are modest in uPA-deficient mice, probably because they still have active tPA. We show that metastasis is strongly and selectively decreased in uPA-deficient mice, suggesting that uPA-directed antimetastatic therapy would be efficacious and have limited side effects. © 2004 Wiley-Liss, Inc.
U2 - 10.1002/ijc.20631
DO - 10.1002/ijc.20631
M3 - Journal article
C2 - 15472905
VL - 113
SP - 525
EP - 532
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -
ID: 1093063