[Frontiers in Bioscience 11, 81-88, January 1, 2006]

[Frontiers in Bioscience 11, 81-88, January 1, 2006]

Changes in laminin isoforms associated with brain tumor invasion and angiogenesis

Julia Y. Ljubimova ¹, Manabu Fujita ¹, Natalya M. Khazenzon ¹, Alexander V. Ljubimov ² & Keith L. Black ¹

1 Maxine Dunitz Neurosurgical Institute, and ²Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, California

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Laminin isoform changes during glioma progression: 3.1. Laminin-8 as a new glioma biomarker; 3.2. Development of in vitro system to block laminin-8; 3.3. Laminin-8 is a predictor of glioma outcome. Clinical data
4. Perspective
5. References

1. ABSTRACT

Laminins are the major constituents of blood vessel basement membranes (BMs). Each laminin is a trimer consisting of three assembled polypeptide chains, a , b and g . More than 15 laminin isoforms are known to date and the expression of specific isoforms may change in certain pathological conditions. Here we show that during progression of glial tumors laminin-9 (a 4b 2g 1) is switched to laminin-8 (a 4b 1g 1), which is dramatically increased in glial brain tumors. Laminin-8 overproduction by glial tumor cells facilitates spread of glioma. Brain tumors with laminin-8 overexpression recur faster after standard treatment and patients have shorter survival time. Laminin-8 may be thus used as a predictor of tumor recurrence, patient survival and as a potential molecular target for glioma therapy.