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Cleaved uPAR; a possible predictor of response in<br />
non-small cell lung cancer treated with chemotherapy<br />
Helle Pappot, Ib Jarle Christensen, Gunilla Høyer-Hansen,<br />
Jens Benn Sørensen<br />
Department of Oncology and Finsen Laboratory, Rigshospitalet, Strandboulevarden 49,<br />
DK-2100 Copenhagen Ø, Denmark<br />
New cancer therapies are emerging in non-small cell lung cancer (NSCLC), and more<br />
treatment options are available even in the disseminated lung cancer setting. This<br />
leaves an urgent need for easy, non-invasive and in-expensive methods to identify<br />
patients who can expect treatment response. We have previously demonstrated<br />
the prognostic importance of components of the plasminogen activation system in<br />
NSCLC. Urokinase (uPA) cleaves its glycolipid-anchored receptor, uPAR. uPAR(I)<br />
is liberated and the cleaved uPAR(II-III) stays on the cell surface. The amounts of<br />
uPAR(II-III) and uPAR(I) may be directly related to the uPA activity and therefore<br />
provide different information than the by ELISA measured total amount of uPAR. In<br />
the present study we investigate the role of different uPAR forms as predictors of<br />
response to chemotherapy (CT) in NSCLC.<br />
Time-resolved fluoroimmunoassays have been designed for the individual measurements<br />
of uPAR(I-III), uPAR(I-III) + uPAR(II-III), and uPAR(I), respectively. The<br />
amounts of uPAR(II-III) can be calculated. These assays were applied on pre-treatment<br />
blood plasma samples from 35 patients diagnosed with stage IIIa-IV NSCLC<br />
and treated with first line CT. Patients received 1-24 cycles of CT (median 9). Patients<br />
were divided due to response to CT (as evaluated by computed tomography scans)<br />
in 1) complete and partial remission (CR+PR) n=14, and 2) no change (NC) n=21.<br />
We found significantly elevated levels of uPAR(I-III), p=0.008, in the pre-treatment<br />
samples from patients having NC to CT compared to patients having CR+PR. A similar<br />
but less significant pattern was found for uPAR(I-III) + uPAR(II-III), p=0.03. The<br />
98p26<br />
correlation between uPAR(I-III) and uPAR(I-III) + uPAR(II-III) was r=0.79, p
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