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Reduction of brain metastases in plasminogen activator inhibitor-1 deficient mice with transgenic ocular tumors
- Source :
- Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2008, epub ahead of print. ⟨10.1093/carcin/bgn204⟩, Carcinogenesis, Carcinogenesis; Vol 29
- Publisher :
- Oxford University Press
-
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.
- Subjects :
- Genetically modified mouse
Cancer Research
Pathology
medicine.medical_specialty
Angiogenesis
Transgene
Blotting, Western
Mice, Transgenic
Retinal Pigment Epithelium
Biology
Metastasis
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Plasminogen Activator Inhibitor 1
medicine
Animals
Oligonucleotide Array Sequence Analysis
030304 developmental biology
Mice, Knockout
0303 health sciences
Brain Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Eye Neoplasms
General Medicine
medicine.disease
Primary tumor
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
chemistry
030220 oncology & carcinogenesis
Plasminogen activator inhibitor-1
Plasminogen activator
Brain metastasis
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2008, epub ahead of print. ⟨10.1093/carcin/bgn204⟩, Carcinogenesis, Carcinogenesis; Vol 29
- Accession number :
- edsair.doi.dedup.....b047f22d0fb9946fced5b49f88ad106a