Antisense oligodeoxynucleotides for urokinase-plasminogen activator receptor have anti-invasive and anti-proliferative effects in vitro and inhibit spontaneous metastases of human melanoma in mice
Authors: Mauro Bologna
Silvia D&#x27;Alessio
Carlo Leonetti
Marco Scarsella
Marco Pucci
Mario Del Rosso
Brett P Monia
Francesca Margheri
Angela Del Rosso
Gabriella Zupi
Gabriella Fibbi
Journal: International Journal of Cancer (2004)
Discipline: CLINICAL MEDICINE
Keywords: uPAR; antisense oligonucleotides; invasion; proliferation; metastasis
Affiliations: Department of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni 50, 50134 Florence, Italy.

Abstract:  We have targeted the urokinase-type plasminogen activator receptor (uPAR) with phosphorothioate antisense oligonucleotides (aODN) in vitro to evaluate the anti-invasive and anti-proliferative effects of uPAR down-regulation, as well as in vivo to evaluate anti-tumor and anti-metastatic activity. aODN-dependent uPAR downregulation in vitro was induced in cells of human melanoma, mammary carcinoma, ovarian carcinoma and SV-40-transformed embryonic lung fibroblasts. uPAR was determined by an antibody-based assay and by semiquantitative polymerase chain reaction. Cell invasion was evaluated by Matrigel invasion assay and cell proliferation by direct cell counting. aODN reduced uPAR, invasion and proliferation in all the treated cell lines. Following aODN treatment, human melanoma cells exhibited a strong decrease of uPAR-dependent ERK1/2 activation and were used in vivo to control metastasis in CD-1 male nude (nu/nu) mice by uPAR aODN injection. 60 mice were injected in the hind leg muscles with a suspension of 10(6) melanoma cells. After 4 days, when a tumor mass of about 350 mg was evident in all the mice injected, 20 mice were treated i.v. with aODN and 20 with dODN at 0.5 mg/day for 5 consecutive days. Twenty control mice were not treated. A second and third cycle of treatment was administered at 2-day intervals. Treatment with aODN resulted into a 78% reduction of lung metastases and 45% reduction of the primary tumor mass with no loss of body weight. Our results suggest to evaluate the utility of uPAR aODN in controlling the metastatic spreading of human melanoma. 

Retracted: No

PubPeer comments:
 Figure 6A. Much more similar than you would expect. https: imgur.com vuJd7PY , 
 Figure 6A. p38 panel. Much more similar after 180 degree rotation than you would expect. https: imgur.com qK5h8GV , 
 2021 Expression of Concern https: onlinelibrary.wiley.com doi 10.1002 ijc.33526 This Expression of Concern is for the above article, published online on 9 February 2004 in Wiley InterScience (www.interscience.wiley.com) and has been published by agreement between the journal Editoru2010inu2010Chief, Prof. Christoph Plass, and Wiley Periodicals LLC. The Expression of Concern has been rendered due to concerns about Figure 6A. In this Western Blot, in the lane of pERK1 2, the bands for 48h and 72h appear similar, with altered contrast and intensity. Further, in the lane for p38, bands 3u20106 appear similar to bands 7u201010 after 180u00b0 rotation. The authors are unable to retrieve the original data due to the time that has elapsed; therefore, duplication of the bands in question can neither be proven nor disproven. All authors had been contacted at their last known email addresses. M.D.R. believes that possible mistakes were unintentional. S.Du2019A., F.M., A.D.R., B.P.M., M.B., C.L., M.S., G.F. did not respond directly, and M.P. and G.Z. could not be reached. The corresponding authors institution at the time of publication has been contacted and we will update this Expression of Concern, if necessary. ,