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Association between laminin-8 and glial tumor grade, recurrence, and patient survival†
Article first published online: 16 JUN 2004
Copyright © 2004 American Cancer Society
Volume 101, Issue 3, pages 604–612, 1 August 2004
How to Cite
Ljubimova, J. Y., Fugita, M., Khazenzon, N. M., Das, A., Pikul, B. B., Newman, D., Sekiguchi, K., Sorokin, L. M., Sasaki, T. and Black, K. L. (2004), Association between laminin-8 and glial tumor grade, recurrence, and patient survival. Cancer, 101: 604–612. doi: 10.1002/cncr.20397
The antibody C4 to the laminin β2 chain produced by Dr. Joshua Sanes was obtained from the Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa (Iowa City, IA), under contract N01-HD-2-3144 from the National Institute of Child Health and Human Development (NICHD).
- Issue published online: 19 JUL 2004
- Article first published online: 16 JUN 2004
- Manuscript Accepted: 29 APR 2004
- Manuscript Revised: 7 APR 2004
- Manuscript Received: 23 JAN 2004
- Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center
- basement membrane;
- extracellular matrix;
- blood vessel;
- human glioma;
- glioblastoma multiforme (GBM);
The authors previously sought to identify novel markers of glioma invasion and recurrence. Their research demonstrated that brain gliomas overexpressed a subset of vascular basement components, laminins, that contained the α4 chain. One of these laminins, laminin-8, was found to be present in highly invasive and malignant glioblastoma multiforme (GBM) (Grade 4 astrocytoma); its expression was associated with a decreased time to tumor recurrence, and it was found in vitro to promote invasion of GBM cell lines.
In the current study, the authors studied glial tumors of different grades in an attempt to correlate laminin-8 expression with tumor recurrence and patient survival. Immunohistochemistry and Western blot analysis were used to detect laminin isoforms of interest.
Using immunohistochemistry and Western blot analysis, the authors confirmed high levels of laminin-8 expression in approximately 75% of the GBM cases examined and in their adjacent tissues, whereas astrocytomas of lower grades expressed for the most part a different isoform, laminin-9, which also was found in low amounts in normal brain tissue and benign meningiomas. Overexpression of laminin-8 in GBM was found to be associated with a statistically significant shorter time to tumor recurrence (P < 0.0002) and a decreased patient survival time (P < 0.015).
The data suggest that laminin-8, which may facilitate tumor invasion, contributes to tumor regrowth after therapy. Laminin-8 may be used as a predictor of tumor recurrence and patient survival and as a potential molecular target for glioma therapy. Cancer 2004. © 2004 American Cancer Society.