title: Brain hyaluronan binding protein inhibits tumor growth.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, Sixth People's Hospital, Medical School, Shanghai Jiaotong University, 200233, China. gaofengc@online.sh.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Man-lin
authors.initials: ML
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: 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
chemical_list: 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