Brain hyaluronan binding protein inhibits tumor growth.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gao
Feng
F
Department of Clinical Laboratory, Sixth People's Hospital, Medical School, Shanghai Jiaotong University, 200233, China. gaofengc@online.sh.cn
Cao
Man-lin
ML
Wang
Lei
L
D000818:Animals; D001923:Brain Chemistry; D002356:Cartilage / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002642:Chick Embryo; D003001:Cloning, Molecular; D042783:Endothelial Cells / Q000166:cytology; D053222:Fas Ligand Protein; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D014162:Transfection
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D006820:Hyaluronic Acid; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases