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Chinese Medical Journal ; (24): 1072-1078, 2004.
Artigo em Inglês | WPRIM | ID: wpr-284848

RESUMO

<p><b>BACKGROUND</b>Great efforts have been made to search for the angiogenic inhibitors in avascular tissues. Several proteins isolated from cartilage have been proved to have anti-angiogenic or anti-tumour effects. Because cartilage contains a great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding proteins (HABP), therefore, we speculated that HABP might be one of the factors regulating vascularization in cartilage or anti-angiogenesis in tumours. The purpose of this research was to evaluate the effects of hyaluronan binding protein on inhibiting tumour growth both in vivo and vitro.</p><p><b>METHODS</b>A unique protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned from human brain cDNA library. MDA-435 human breast cancer cell line was chosen as a transfectant. The in vitro underlying mechanisms were investigated by determining the possibilities of MDA-435/b-HABP colony formation on soft agar, the effects of the transfectant on the proliferation of endothelial cells and the expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos and nude mice.</p><p><b>RESULTS</b>Colony formation assay revealed that the colonies formed by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than that of MDA-435 alone.</p><p><b>CONCLUSIONS</b>Human brain hyaluronan binding protein (b-HABP) may represent a new kind of naturally existing anti-tumour substance. This brain-derived glycoprotein may block tumour growth by inducing apoptosis of cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting proliferation of endothelial cells.</p>


Assuntos
Animais , Embrião de Galinha , Humanos , Camundongos , Química Encefálica , Cartilagem , Fisiologia , Caspase 3 , Caspases , Linhagem Celular Tumoral , Clonagem Molecular , Células Endoteliais , Biologia Celular , Proteína Ligante Fas , Receptores de Hialuronatos , Genética , Fisiologia , Ácido Hialurônico , Metabolismo , Glicoproteínas de Membrana , Neoplasias Experimentais , Terapêutica , Neovascularização Patológica , Transfecção
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