This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khazenzon, N. M. Articles by Ljubimova, J. Y. Search for Related Content PubMed PubMed Citation Articles by Khazenzon, N. M. Articles by Ljubimova, J. Y.

¹ Maxine Dunitz Neurosurgical Institute and ² Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA; ³ Institute for Protein Research, Osaka University, Osaka, Japan; ⁴ Department of Pathology, Jubileum Institute, Lund University, Lund, Sweden; ⁵ Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland

Requests for reprints: Julia Y. Ljubimova, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800-E, Los Angeles, CA 90048. Phone: (310) 423-0834; Fax: (310) 423-0810. E-mail: ljubimovaj{at}cshs.org

Using gene array technology, we recently observed for the first time an up-regulation of laminin 4 chain in human gliomas. The data were validated by semiquantitative reverse transcription-PCR for RNA expression and immunohistochemistry for protein expression. Moreover, increase of the 4 chain-containing laminin-8 correlated with poor prognosis for patients with brain gliomas. Therefore, we hypothesized that inhibition of laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino) against chains of laminin-8 could slow or stop the spread of glioma and its recurrence and thus might be a promising approach for glioma therapy. We next sought to establish an in vitro model to test the feasibility of this approach and to optimize conditions for Morpholino treatment. To develop a model, we used human glioblastoma multiforme cell lines M059K and U-87MG cocultured with normal human brain microvascular endothelial cells (HBMVEC). Using Western blot analysis and immunohistochemistry, we confirmed that antisense treatment effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides against both 4 and ß1 chains of laminin-8 were able to block significantly the invasion of cocultures through Matrigel. On average, the invasion was blocked by 62% in cocultures of U-87MG with HBMVEC and by 53% in cocultures of M059K with HBMVEC. The results show that laminin-8 may contribute to glioma progression and recurrence not only as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.

Grant support: Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, and Arrogene, Inc.

² American Cancer Society, Brain and Spinal Cord Tumors in Adults (http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_brain_and_spinal_cord_tumors_3?sitearea=C. RI).

Received 1/10/03; revised 6/18/03; accepted 7/22/03.

This article has been cited by other articles:

				A. K. Berfield, K. M. Hansen, and C. K. Abrass Rat glomerular mesangial cells require laminin-9 to migrate in response to insulin-like growth factor binding protein-5 Am J Physiol Cell Physiol, October 1, 2006; 291(4): C589 - C599. [Abstract] [Full Text] [PDF]

				M. Saghizadeh, A. A. Kramerov, J. Tajbakhsh, A. M. Aoki, C. Wang, N.-N. Chai, J. Y. Ljubimova, T. Sasaki, G. Sosne, M. R. J. Carlson, et al. Proteinase and Growth Factor Alterations Revealed by Gene Microarray Analysis of Human Diabetic Corneas Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3604 - 3615. [Abstract] [Full Text] [PDF]

				M. Maatta, R. Butzow, J. Luostarinen, N. Petajaniemi, T. Pihlajaniemi, S. Salo, K. Miyazaki, H. Autio-Harmainen, and I. Virtanen Differential Expression of Laminin Isoforms in Ovarian Epithelial Carcinomas Suggesting Different Origin and Providing Tools for Differential Diagnosis J. Histochem. Cytochem., October 1, 2005; 53(10): 1293 - 1300. [Abstract] [Full Text] [PDF]