Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors

✓ The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

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The distribution of nuclear DNA from human brain-tumor cells

Journal of Neurosurgery ◽

10.3171/jns.1978.49.1.0013 ◽

1978 ◽

Vol 49 (1) ◽

pp. 13-21 ◽

Cited By ~ 80

Author(s):

Takao Hoshino ◽

Kazuhiro Nomura ◽

Charles B. Wilson ◽

Kathy D. Knebel ◽

Joe W. Gray

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Human Brain ◽

Dna Synthesis ◽

Tumor Cells ◽

Malignant Gliomas ◽

Benign Tumors ◽

Low Grade ◽

Human Brain Tumor ◽

Large Variability

✓ Flow cytometry (FCM) is a technique that measures the quantity of DNA contained in individual nuclei and records a frequency distribution of the DNA content per nucleus in the sampled cell population. Nuclei from a variety of human brain-tumor types were isolated by means of tissue grinding, purified by centrifugation through 40% sucrose (15 minutes at 4000 rpm), fixed with 10% formalin, stained with acriflavin-Feulgen, and analyzed by FCM. Profiles of DNA distribution in histologically benign tumors, such as meningiomas, pituitary adenomas, neuroblastomas, and low-grade astrocytomas, revealed a large diploid population (2C) with a few nuclei in DNA synthesis, as well as a small premitotic population (G2 cells) that contains a 4C DNA complement. In contrast, malignant gliomas, including glioblastomas, consist of more cells in DNA synthesis; these tumor cells show a highly variable distribution of ploidy consisting not only of diploid, and/or aneuploid, but also of triploid, tetraploid, and possibly octaploid populations. Also, a large variability between different regions of each tumor was always observed. In contrast, metastatic brain tumors, despite the fact that they contain a considerable number of cells undergoing DNA synthesis, demonstrate little variability within each individual tumor. The ability to rapidly characterize the cell populations of human brain tumors with FCM may enhance the effectiveness of their clinical management.

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Plasminogen activator activity and molecular weight patterns in human brain tumors

Journal of Neurosurgery ◽

10.3171/jns.1988.68.1.0073 ◽

1988 ◽

Vol 68 (1) ◽

pp. 73-79 ◽

Cited By ~ 32

Author(s):

Raymond Sawaya ◽

Robert Highsmith

Keyword(s):

Molecular Weight ◽

Brain Tumor ◽

Brain Tumors ◽

Human Brain ◽

Plasminogen Activator ◽

Malignant Tumors ◽

Benign Tumors ◽

Normal Brain ◽

Human Brain Tumor ◽

Content Type

✓ Fresh human brain-tumor samples were assayed for their plasminogen activator (PA) content. Specific molecular weight patterns were identified for each of five common brain tumors and for normal brain, suggesting a cell-specific origin of the various PA forms. Malignant tumors contained higher PA activity and a larger number of molecular weight patterns than benign tumors, with the exception of acoustic neurinomas. Irradiated tumors contained lower PA activity than nonirradiated tumors. Finally, a slight but definite correlation between brain edema and PA activity was detected. The future role of brain-tumor PA's for diagnostic and therapeutic purposes is discussed.

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