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

S. S. Lakka, R. Rajagopal, M. K. Rajan, P. M. Mohan, Y. Adachi, D. H. Dinh, W. C. Olivero, M. Gujrati, F. Ali-Osman, J. A. Roth, W. K A Yung, A. P. Kyritsis, J. S. Rao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1087-1093
Number of pages7
JournalClinical Cancer Research
Volume7
Issue number4
StatePublished - Jan 1 2001

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Urokinase Plasminogen Activator Receptors
Adenoviridae
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Cell Line
Genes
Neoplasms
Lung Neoplasms
Reticulocytes
Infection
Cytomegalovirus
Nude Mice
Tail
Veins
Western Blotting
RNA
Rabbits
Viruses
Lung
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. / Lakka, S. S.; Rajagopal, R.; Rajan, M. K.; Mohan, P. M.; Adachi, Y.; Dinh, D. H.; Olivero, W. C.; Gujrati, M.; Ali-Osman, F.; Roth, J. A.; Yung, W. K A; Kyritsis, A. P.; Rao, J. S.

In: Clinical Cancer Research, Vol. 7, No. 4, 01.01.2001, p. 1087-1093.

Research output: Contribution to journalArticle

Lakka, SS, Rajagopal, R, Rajan, MK, Mohan, PM, Adachi, Y, Dinh, DH, Olivero, WC, Gujrati, M, Ali-Osman, F, Roth, JA, Yung, WKA, Kyritsis, AP & Rao, JS 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', Clinical Cancer Research, vol. 7, no. 4, pp. 1087-1093.
Lakka, S. S. ; Rajagopal, R. ; Rajan, M. K. ; Mohan, P. M. ; Adachi, Y. ; Dinh, D. H. ; Olivero, W. C. ; Gujrati, M. ; Ali-Osman, F. ; Roth, J. A. ; Yung, W. K A ; Kyritsis, A. P. ; Rao, J. S. / Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 4. pp. 1087-1093.
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AU - Dinh, D. H.

AU - Olivero, W. C.

AU - Gujrati, M.

AU - Ali-Osman, F.

AU - Roth, J. A.

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