High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma.
OBJECTIVE
Extra-neural metastases from glioblastoma multiforme (GBM) are rare. Because gelatinases-A and -B have been implicated in tumor invasion/metastasis in non-neural tumors, we compared the expression of gelatinase-A and -B in 2 patients (both had a prior craniotomy performed) with extraneural metastases from GBM to expression levels in 24 other gliomas; 15 non-metastatic GBMs, 9 other lower grade gliomas, and 7 normal brain tissues.


METHODS
The intracerebral tumor from both patients, patient # 1's extraneural metastases, 24 other gliomas, 1 sample of reactive astrocytes and 7 normal brain tissues were studied using gelatin zymography. The active form of gelatinases was confirmed by co-migration after activation with APMA.


RESULTS
Expression of the latent form of gelatinase-A correlated with glioma grade (r = 0.486; p = 0.0053). Active gelatinase-A was found only in the 2 GBMs with extraneural metastases and patient # 1's cervical metastases. In contrast, latent gelatinase-B levels correlated more strongly with histologic grade (r = 0.577; p = 0.0009) (higher levels with higher grades). Very high levels of gelatinase-B were seen in both GBMs with extraneural metastases, a cervical extraneural metastases, and 2 GBMs without metastases.


CONCLUSIONS
We observed that gelatinases-A and -B are present in most gliomas but we found active gelatinase-A only in the GBMs with extraneural metastases suggesting that the active form of this enzyme may determine the metastatic potential of GBMs. We propose that high levels of gelatinolytic activities are associated with intracerebral invasion and rarely, metastases of GBMs.
Forsyth
P A
PA
Department of Medicine, Tom Baker Cancer Centre, Foothills Hospital, The University of Calgary, Alberta, Canada.
Laing
T D
TD
Gibson
A W
AW
Rewcastle
N B
NB
Brasher
P
P
Sutherland
G
G
Johnston
R N
RN
Edwards
D R
DR
D000328:Adult; D001932:Brain Neoplasms / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D017809:Fatal Outcome; D018093:Gelatinases / Q000378:metabolism*; D005909:Glioblastoma / Q000201:enzymology* / Q000556:secondary*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000556:secondary; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D009918:Orbital Neoplasms / Q000201:enzymology / Q000556:secondary; D012888:Skull Neoplasms / Q000201:enzymology / Q000556:secondary; D014134:Tracheal Neoplasms / Q000201:enzymology / Q000556:secondary
D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9