التفاصيل البيبلوغرافية
العنوان:
Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinases-1 in the liver: efficient protection against T-cell lymphoma and colon carcinoma metastasis
المؤلفون:
Rama Khokha , Charlotte Kopitz , Sefer Elezkurtaj , Achim Krüger , Matthias J.E. Arlt , Andrew H. Baker , Bernd Gansbacher , Karsten Brand , Martina Anton , Alejandra Perez-Cantó
المصدر:
The Journal of Gene Medicine . 6:1228-1237
بيانات النشر:
Wiley, 2004.
سنة النشر:
2004
مصطلحات موضوعية:
Colorectal cancer , Genetic enhancement , Matrix metalloproteinase , Biology , medicine.disease , Lymphoma , Metastasis , Transduction (genetics) , Cell culture , Drug Discovery , Immunology , Genetics , medicine , Cancer research , Molecular Medicine , T-cell lymphoma , Molecular Biology , Genetics (clinical)
الوصف:
Background Matrix metalloproteinases (MMPs) are critical for metastasis of tumor cells. Tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural MMP inhibitor, was shown to reduce metastasis in different models. Here, we investigated whether increased TIMP-1 levels in the liver achieved by adenoviral gene transfer will effectively inhibit liver metastasis of two independent tumor cell lines. Method TIMP-1 was transferred with adenoviral vectors into the livers of DBA/2 and Balb/c mice, which were subsequently challenged by hematogenous experimental metastases of the T-cell lymphoma cell line L-CI.5s or the colorectal carcinoma cell line CT-26, respectively. Results MMP-9 expression in the liver was induced upon metastasis in both tumor types. Adenoviral gene transfer led to high transduction efficacy as indicated by lacZ expression in 60% of hepatocytes. TIMP-1, a key inhibitor of MMP-9, was expressed at 105-fold higher levels by adenoviral gene transfer as compared with levels achieved in TIMP-1 transgenic mice, previously shown to be inefficient to reduce T-cell lymphoma metastasis. High local and systemic (serum) levels of TIMP-1 led to substantial (94%) reduction of T-cell lymphoma and colorectal carcinoma (73%) experimental liver metastasis. Conclusions Adenoviral gene transfer led to systemic and local TIMP-1 levels sufficient to inhibit metastasis of a highly aggressive T-cell lymphoma, pointing at the requirement of threshold levels for effective anti-metastatic efficacy. This approach was also efficient in a colon carcinoma solid tumor model. We propose that viral gene transfer of TIMP-1 can provide a suitable defense strategy to prevent metastatic spread to the liver. Copyright © 2004 John Wiley & Sons, Ltd.
تدمد:
1099-498X
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_________::8036bd6c2afd4989726fa620cf3f42fbTest https://doi.org/10.1002/jgm.637Test
حقوق:
CLOSED
رقم الانضمام:
edsair.doi...........8036bd6c2afd4989726fa620cf3f42fb
قاعدة البيانات:
OpenAIRE
