Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors.

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  • Additional Information
    • Source:
      Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2180 (Electronic) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Irl Press At Oxford University Press
      Original Publication: [New York, IRL Press]
    • Subject Terms:
      Brain Neoplasms/*prevention & control ; Brain Neoplasms/*secondary ; Eye Neoplasms/*pathology ; Plasminogen Activator Inhibitor 1/*physiology; Animals ; Blotting, Western ; Brain Neoplasms/genetics ; Eye Neoplasms/genetics ; Mice ; Mice, Knockout ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; Plasminogen Activator Inhibitor 1/genetics ; Retinal Pigment Epithelium/pathology ; Reverse Transcriptase Polymerase Chain Reaction
    • Abstract:
      Plasminogen activator inhibitor-1 is known to play a paradoxical positive role in tumor angiogenesis, but its contribution to metastatic spread remains unclear. We studied the impact of plasminogen activator inhibitor (PAI)-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to brain metastasis (TRP-1/SV40 Tag mice). PAI-1 deficiency did not affect primary tumor growth or vascularization, but was associated with a smaller number of brain metastases. Brain metastases were found to be differentially distributed between the two genotypes. PAI-1-deficient mice displayed mostly secondary foci expanding from local optic nerve infiltration, whereas wild-type animals displayed more disseminated nodules in the scissura and meningeal spaces. SuperArray GEarray analyses aimed at detecting molecules potentially compensating for PAI-1 deficiency demonstrated an increase in fibroblast growth factor-1 (FGF-1) gene expression in primary tumors, which was confirmed by reverse transcription-polymerase chain reaction and western blotting. Our data provide the first evidence of a key role for PAI-1 in a spontaneous model of metastasis and suggest that angiogenic factors, such as FGF-1, may be important for primary tumor growth and may compensate for the absence of PAI-1. They identify PAI-1 and FGF-1 as important targets for combined antitumor strategies.
    • Accession Number:
      0 (Plasminogen Activator Inhibitor 1)
    • Publication Date:
      Date Created: 20080830 Date Completed: 20081124 Latest Revision: 20081103
    • Publication Date:
      20231215
    • Accession Number:
      10.1093/carcin/bgn204
    • Accession Number:
      18753414