| A double three-step theory of brain metastasis in mice: the role of the pia mater and matrix metalloproteinases. | |
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MedLine Citation:
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PMID: 17493010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The brain is frequently affected by the spread of lung cancer, and haematogenous metastasis is a common route to brain metastasis. We therefore developed an isogenic brain metastasis model of lung cancer to use the Lewis lung carcinoma cell line and analysed dynamics of neoplastic cells after extravasation. Histological analysis revealed two characteristic patterns: metastatic foci exhibiting an angiocentric pattern were designated 'perivascular proliferations'; neoplastic cells infiltrating the brain parenchyma were designated 'invasive proliferations'. Electron microscopic observation of perivascular proliferations showed that neoplastic cells were confined to the perivascular space. In invasive proliferations, however, fragments of collagen fibre were observed in the gaps between neoplastic cells, indicating that the neoplastic cells had disintegrated the pia-glial membrane. We analysed the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 by using both immunohistochemical analysis and real-time polymerase chain reaction analysis. MMP-2 expression was significantly higher in invasive proliferations. MMP-9 expression was significantly higher in day 7, but there was no significant difference in day 11. The pia-glial membrane and perivascular space are the barriers that neoplastic cells must overcome to infiltrate the brain. In conclusion, our findings suggest that brain metastasis requires two distinct processes. |
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Authors:
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N Saito; T Hatori; N Murata; Z-A Zhang; F Ishikawa; H Nonaka; S Iwabuchi; H Samejima |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Neuropathology and applied neurobiology Volume: 33 ISSN: 0305-1846 ISO Abbreviation: Neuropathol. Appl. Neurobiol. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-11 Completed Date: 2007-07-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7609829 Medline TA: Neuropathol Appl Neurobiol Country: England |
Other Details:
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Languages: eng Pagination: 288-98 Citation Subset: IM |
Affiliation:
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Second Department of Neurosurgery, Toho University School of Medicine, Tokyo, Japan. bsaitob@med.toho-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Neoplasms / blood supply, enzymology*, secondary* Carcinoma, Lewis Lung / enzymology*, secondary* Immunohistochemistry Lasers Male Matrix Metalloproteinases / metabolism* Mice Microdissection Neoplasm Invasiveness Pia Mater / ultrastructure* Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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EC 3.4.24.-/Matrix Metalloproteinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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