Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas.
Recent studies suggest that cysteine proteinase cathepsin L is involved in the process of tumor invasion and metastasis. We examined cathepsin L activity in brain tumor tissue samples by an enzymatic assay, and cathepsin L protein content by enzyme-linked immunoadsorbent assays and Western blotting to determine whether increased levels of cathepsin L correlate with the progression of human gliomas. Native and acid-activatable cathepsin L activities were highest in glioblastomas followed by anaplastic astrocytomas and were lowest in low-grade gliomas and normal brain tissues. Significantly higher amounts of an M(r) 29,000 cathepsin L were present in glioblastomas and anaplastic astrocytomas than in normal brain tissues and low-grade glioma tissue extracts. Using specific antibodies to cathepsin L, we also studied its cellular distribution by immunohistochemical procedures. Higher diffuse cathepsin L immunoreactivity was found in glioblastomas than in low-grade gliomas and normal brain tissue samples. Finally, the addition of cathepsin L antibody inhibits the invasion of glioblastoma cell lines through Matrigel invasion assay. These results suggest the expression of cathepsin L is dramatically upregulated in malignant gliomas and correlates with the malignant progression of human gliomas in vivo.
Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
M
M
Sivaparvathi
M
M
Yamamoto
G L
GL
Nicolson
Z L
ZL
Gokaslan
G N
GN
Fuller
L A
LA
Liotta
R
R
Sawaya
J S
JS
Rao
D000906:Antibodies / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay; D005909:Glioblastoma / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness
D000906:Antibodies; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L