1.
Ljubimova, JY, et al.
(författare)
Association between laminin-8 and glial tumor grade, recurrence, and patient survival
2004
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 101:3, s. 604-612
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND. 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 alpha4 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. METHODS. 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. RESULTS. 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). CONCLUSIONS. 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.
2.
Masocha, W, et al.
(författare)
Cerebral vessel laminins and IFN-gamma y define Trypanosoma brucei brucei penetration of the blood-brain barrier
2004
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 114:5, s. 689-694
Tidskriftsartikel (refereegranskat) abstract
Subspecies of Trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. We investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence T. brucei neuroinvasion. Migration of a rodent pathogenic T. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in IFN-gamma(-/-), IFN-gamma receptor(-/-) (IFN-gammaR(-/-)), IL-12p40(-/-), and recombinant activating gene-1(-/-) (RAG-1(-/-)) mice as compared with their WT littermates despite higher levels of parasitemia in the mutant strains. Parasites accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the brains of IFN-gamma(-/-), IFN-gammaR(-/-), and RAG-1(-/-) mice. This accumulation occurred around endothelial basement membranes containing the laminin alpha4 chain, while blood vessels showing robust laminin alpha5 chain immunostaining were not associated with parasite infiltration. The number of CD4(+) and CD8(+) T cells infiltrating the brain parenchyma was also reduced in the IFN-gamma(-/-) and IFN-gammaR(-/-) mice. Our findings suggest that lymphocyte-derived IFN-gamma facilitates trypanosome penetration across cerebral blood vessels and that the site of penetration is determined by the composition of the basement membranes of these vessels.
3.
Minuth, W, et al.
(författare)
Generation of renal tubules at the interface of an artificial interstitium
2004
Ingår i: Cellular Physiology and Biochemistry. - : S. Karger AG. - 1015-8987 .- 1421-9778. ; 14:4-6, s. 387-394
Tidskriftsartikel (refereegranskat) abstract
During kidney development a multitude of tubular portions is formed. Little knowledge is available by which cellbiological mechanism a cluster of embryonic cells is able to generate the threedimensional structure of a tubule. However, this know-how is most important in tissue engineering approaches such as the generation of an artificial kidney module or for the therapy of renal diseases using stem cells. To obtain cellbiological insights in parenchyme development we elaborate a new technique to generate under in vitro conditions renal tubules derived from the embryonic cortex of neonatal rabbits. The aim of the experiments is to establish a specific extracellular environment allowing optimal threedimensional development of renal tubules under serum-free culture conditions. In the present paper we demonstrate features of the renal stem cell niche and show their isolation as intact microcompartiments for advanced tissue culture. Perfusion culture in containers exhibiting a big dead fluid volume results in the development of a flat collecting duct (CD) epithelium at the surface of the tissue explant. In contrast, by fine-tuning the dead fluid volume within a perfusion culture container by an artificial interstitium made of a polyester fleece shows the generation of tubules. It is an up to date unknown morphogenetic information which tells the cells to form tubular structures. Copyright (C) 2004 S. Karger AG, Basel.
4.
Zhou, ZJ, et al.
(författare)
Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice
2004
Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 64:12, s. 4059-4063
Tidskriftsartikel (refereegranskat) abstract
Laminin-8 (alpha4beta1gamma1) is one of the major laminin isoforms expressed in vascular endothelial basement membranes. Here we show that deletion of laminin-8 in mice affects angiogenesis under pathological conditions. Murine tumor models used in laminin alpha4-deficient mice results in hyperneovascularization and significant promotion of tumor growth and metastasis. The higher tumor growth rates in mutant mice correlate with decreased tumor cell apoptosis. Depletion of laminin alpha4 chain may alter the structure of vascular basement membranes, leading to increased angiogenesis. Our data suggest that the laminin-8 plays a critical role in the regulation of pathological angiogenesis.
