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HOXB7: a key factor for tumor-associated angiogenic switch.
A Carè1, F Felicetti, E Meccia
1Department of Hematology and Oncology, Istituto Superiore di Sanità, 00161 Rome. a.care@iss.it
Cancer Research
|August 28, 2001
Summary
Homeobox B7 (HOXB7) promotes tumor progression by up-regulating proangiogenic factors like vascular endothelial growth factor and matrix metalloproteinase-9. Targeting HOXB7 may inhibit tumor angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Altered homebox (HOX) gene expression, specifically HOXB7, is linked to tumor progression.
- HOXB7 has been previously shown to transactivate basic fibroblast growth factor.
Purpose of the Study:
- To investigate if HOXB7 induces other genes related to neoangiogenesis and tumor invasion beyond basic fibroblast growth factor.
- To evaluate the functional implications of HOXB7-induced gene expression on tumor growth and vascularization.
Main Methods:
- Expression analysis of growth factors, receptors, and matrix-degrading enzymes in HOXB7-transduced SkBr3 cells.
- In vitro co-culture assay with endothelial cells in a 3D matrix.
- In vivo xenograft studies in athymic nude mice.
- Immunohistochemical analysis (CD-31, CD-34) for tumor vascularization.
Main Results:
- HOXB7 transduction up-regulated vascular endothelial growth factor, melanoma growth-stimulatory activity/growth-related oncogene alpha, interleukin-8, and angiopoietin-2.
- HOXB7 abrogated angiopoietin-1 expression and induced matrix metalloproteinase-9 (MMP-9).
- HOXB7-transduced cells delayed endothelial cell differentiation in vitro and formed tumors in vivo, exhibiting increased vascularization compared to controls.
Conclusions:
- HOXB7 is a key factor that up-regulates multiple proangiogenic stimuli, including growth factors and MMP-9.
- HOXB7 promotes neoangiogenesis and tumor invasion.
- The HOXB7 gene or protein represents a potential therapeutic target for inhibiting tumor-associated neoangiogenesis.