title: Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas.
abstract: Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded astrocytomas and compared with tumor grade and overall patient survival. Moreover, double immunofluorescence stainings were performed with LAMP-1 and the astrocytic marker GFAP and the putative stem cell marker CD133 on ten glioblastomas. Most tumors expressed the LAMP-1 protein in the cytoplasm of the tumor cells, while the blood vessels were positive in all tumors. The percentage of LAMP-1 positive tumor cells and staining intensities increased with tumor grade but variations in tumors of the same grade were also found. No association was found between LAMP-1 expression and patient overall survival in the individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem cells. Targeting of lysosomes may be a promising novel therapeutic strategy against this highly malignant neoplasm.
authors.affiliation: Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark.
authors.forename: Stine S
authors.initials: SS
authors.lastname: Jensen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Aaberg-Jessen
authors.forename: Karina G
authors.initials: KG
authors.lastname: Christensen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Kristensen
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D001254:Astrocytoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051907:Lysosomal Membrane Proteins / Q000032:analysis*; D008247:Lysosomes / Q000737:chemistry* / Q000473:pathology; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000737:chemistry; D010455:Peptides / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D051907:Lysosomal Membrane Proteins; D010455:Peptides; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C000606023:PROM1 protein, human
keywords: LAMP-1; glioblastomas; immunohistochemistry; lysosomes; tumor stem cells