Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy.
Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of the leptin system in brain tumor development remains unknown. We screened 87 human brain tumor biopsies using immunohistochemistry and detected leptin and ObR in 55.2% and 60.9% cases, respectively. In contrast, leptin and ObR were absent in 14 samples of normal brain tissue. The presence of leptin correlated with ObR with overall concordance 80.5%. The leptin/ObR system was highly expressed in glioblastomas and anaplastic astrocytomas, while lower expression of both markers was noted in low-grade astrocytomas and gangliogliomas. The association between leptin/ObR and the degree of tumor malignancy was highly significant (P < 0.001). Using double immunofluorescence of glioblastoma tissues, we found co-expression of leptin with ObR and with the proliferation marker Ki-67 in 87% and 64% of cells, respectively. The leptin/ObR-positive tissues also expressed activated forms of STAT3 and Akt. In line with this finding, ObR-positive glioblastoma cells responded to leptin with cell growth and induction of the STAT3 and Akt pathways as well as inactivation of the cell cycle suppressor Rb. In summary, our data demonstrate that the leptin/ObR system is expressed in malignant brain tumors and might be involved in tumor progression.
Riolfi
Mirko
M
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA.
Ferla
Rita
R
Del Valle
Luis
L
Piña-Oviedo
Sergio
S
Scolaro
Laura
L
Micciolo
Rocco
R
Guidi
Micol
M
Terrasi
Marianna
M
Cetto
Gian Luigi
GL
Surmacz
Eva
E
D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D019394:Ki-67 Antigen; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051058:Oncogene Protein v-akt