You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Targeting of plasminogen activation in MMTV-PymT<br />
transgenic breast cancer and in skin wound healing<br />
John Rømer, Annika Jögi, Ida K. Lund, Kasper Almholt,<br />
Gunilla Høyer-Hansen, Leif R. Lund, Keld Danø<br />
Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, 2100 Copenhagen, Denmark<br />
uPA deficiency in mice is associated with >7-fold reduction of lung metastasis in the<br />
MMTV-PymT transgenic breast cancer model as well as reduced dissemination to<br />
brachial lymph nodes. In contrast, tumor incidence, latency, growth rate and final<br />
primary tumor burden are not significantly affected by uPA deficiency in this model<br />
(Almholt et al., 2005). In order to test whether it is possible to reduce metastasis<br />
in the MMTV-PymT model by pharmacological blocking of uPA-activity, we have<br />
developed a number of monoclonal antibodies (mAbs) directed against mouse uPA.<br />
These mAbs were generated in uPA-deficient mice and selected in vitro for their ability<br />
to block uPA-activity. Studies of skin wound healing in mice double-deficient in uPA<br />
and tPA have revealed that wound closure and epidermal migration are significantly<br />
impaired in uPA;tPA-deficient mice. Based on this finding we are currently testing the<br />
effect of an uPA-neutralising mAb in vivo in skin wound healing studies. Anti-uPA<br />
mAb was administered systemically to tPA-deficient mice with incisional wounds,<br />
which led to a dose-dependent impairment of skin repair. At the highest doses of<br />
anti-uPA mAb the effect on skin wound healing was almost identical to that seen in<br />
uPA;tPA double-deficient mice. This indicates that the present monoclonal antibody<br />
will be suitable for testing its anti-metastatic effect in the MMTV-PymT transgenic<br />
breast cancer model.<br />
l37<br />
55
Change language