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Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma.
- Source :
-
Clinical & experimental metastasis [Clin Exp Metastasis] 2010 Oct; Vol. 27 (7), pp. 539-47. Date of Electronic Publication: 2010 Jul 10. - Publication Year :
- 2010
-
Abstract
- Cancer cells metastasize by entering the lymphatic system. Regional lymph-node dissemination is the first detectable step in the metastasis of oral squamous cell carcinoma (SCC) and is highly correlated to the prognosis of the disease. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis and lymphangiogenesis by directly binding to hypoxia response element (HRE) and serum response element (SRE). In our study we used the cell line NR-S1M, a mouse SCC model with a high rate of lymph-node metastasis. Into these cells we transfected the expression-plasmid coding for full-length mouse CSDA. Of importance, we showed that overexpression of CSDA significantly inhibits the production of VEGF-A and VEGF-C in NR-S1M cells. The overexpression of CSDA in NR-S1M cells inhibited tumor growth, inhibited regional lymph-node metastasis, and reduced the density of blood vessels and lymphatic vessels in the primary tumors in vivo. Our results support the hypothesis that VEGF-A and VEGF-C are crucial regulators of angiogenesis and lymphangiogenesis in NR-S1M cells. Therefore, they are promising targets for CSDA overexpression gene therapy to inhibit tumor growth and lymph-node metastasis in SCC.
- Subjects :
- Animals
CCAAT-Enhancer-Binding Proteins metabolism
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Female
Heat-Shock Proteins metabolism
Immunohistochemistry
Mice
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A metabolism
CCAAT-Enhancer-Binding Proteins physiology
Carcinoma, Squamous Cell pathology
Disease Models, Animal
Heat-Shock Proteins physiology
Lymphatic Metastasis
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7276
- Volume :
- 27
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical & experimental metastasis
- Publication Type :
- Academic Journal
- Accession number :
- 20623179
- Full Text :
- https://doi.org/10.1007/s10585-010-9343-y