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Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines.

Publication ,  Journal Article
Lakka, SS; Rajagopal, R; Rajan, MK; Mohan, PM; Adachi, Y; Dinh, DH; Olivero, WC; Gujrati, M; Ali-Osman, F; Roth, JA; Yung, WK; Kyritsis, AP; Rao, JS
Published in: Clin Cancer Res
April 2001

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an invasive human lung cancer cell line that produces high levels of uPAR, resulted in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the multiplicity of infection from 25 to 200 caused a corresponding decrease in the level of uPAR protein within 5 days of treatment, as shown by Western blot analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR-infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70% decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the levels in cells of mock and vector controls. The Matrigel invasion assay showed the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased by 70% relative to mock- and vector-infected controls. Infection of tumor cells with Ad-uPAR before implantation significantly reduced the incidence of lung metastasis by 85% as compared with the control virus-infected cells injected into nude mice through the tail vein. Our collective results show that the uPAR system is a potential target of treatment for lung cancers.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

April 2001

Volume

7

Issue

4

Start / End Page

1087 / 1093

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Urokinase Plasminogen Activator
  • Receptors, Cell Surface
  • RNA, Messenger
  • Protein Biosynthesis
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lakka, S. S., Rajagopal, R., Rajan, M. K., Mohan, P. M., Adachi, Y., Dinh, D. H., … Rao, J. S. (2001). Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines. Clin Cancer Res, 7(4), 1087–1093.
Lakka, S. S., R. Rajagopal, M. K. Rajan, P. M. Mohan, Y. Adachi, D. H. Dinh, W. C. Olivero, et al. “Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines.Clin Cancer Res 7, no. 4 (April 2001): 1087–93.
Lakka SS, Rajagopal R, Rajan MK, Mohan PM, Adachi Y, Dinh DH, Olivero WC, Gujrati M, Ali-Osman F, Roth JA, Yung WK, Kyritsis AP, Rao JS. Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines. Clin Cancer Res. 2001 Apr;7(4):1087–1093.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

April 2001

Volume

7

Issue

4

Start / End Page

1087 / 1093

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Urokinase Plasminogen Activator
  • Receptors, Cell Surface
  • RNA, Messenger
  • Protein Biosynthesis
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice