Changes in laminin isoforms associated with brain tumor invasion and angiogenesis.
Laminins are the major constituents of blood vessel basement membranes (BMs). Each laminin is a trimer consisting of three assembled polypeptide chains, alpha, beta and gamma. 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 (alpha4beta2gamma1) is switched to laminin-8 (alpha4beta1gamma1), 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.
Ljubimova
Julia Y
JY
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. ljubimovaj@cshs.org
Fujita
Manabu
M
Khazenzon
Natalya M
NM
Ljubimov
Alexander V
AV
Black
Keith L
KL
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology; D005910:Glioma / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012008:Recurrence; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D007797:Laminin; D016376:Oligonucleotides, Antisense; C110308:laminin 8; C404084:laminin 9