Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis.
Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis.
复制标题
鉴定出一种新型膜蛋白 HP59，具有作为肿瘤血管生成靶标的治疗潜力。
作者：
Changlin Fu;Smriti Bardhan;Nicolae D Cetateanu;B. Wamil;Yufen Wang;He;Ergang Shi;Clint Carter;Christo Venkov;F. Yakes;David L. Page;R. Lloyd;R. Mernaugh;C. Hellerqvist;H
CM101是一种从新生儿病原体B组链球菌的培养基中分离的多糖，其靶向病理性血管生成并抑制小鼠和人的肿瘤生长。CM101还靶向新生儿肺和成年绵羊肺内皮细胞。从绵羊肺内皮细胞cDNA文库中分离到一个编码与CM101相互作用的跨膜蛋白的基因。该基因称为sp55，编码495个氨基酸的多肽。用含有sp 55的载体转染的COS-7细胞以浓度依赖性方式表达SP 55蛋白结合的CM 101。稳定转染的CHO细胞也结合CM101。从人胎肺cDNA文库中分离出相应的人基因hp59，在495个氨基酸上与SP55具有86%的预测同一性。免疫组化显示HP59蛋白存在于肺、乳腺、结肠和卵巢的病理性肿瘤血管中，但不存在于正常血管中，表明该蛋白可能对病理性血管生成至关重要。hp59基因和/或HP59蛋白在多种正常组织中不表达，但在人胎肺中显著表达，与新生儿B组链球菌感染的病理生理学一致。用HP59和SP55肽免疫的小鼠显示出肿瘤生长的显著减弱。免疫有效地抑制了肿瘤血管生成和血管生成过程，如缺乏HP 59和CD 34阳性血管所证明的。这些结果和免疫组化数据表明CM101靶蛋白HP59作为药物靶标和作为针对病理性血管生成的疫苗两者的治疗潜力。
CM101, a polysaccharide isolated from the culture medium of Group B streptococcus, a neonatal pathogen, targets pathological angiogenesis and inhibits tumor growth in mice and humans. CM101 also targets neonatal lung and adult sheep lung endothelial cells. A gene encoding a transmembrane protein that interacts with CM101 was isolated from a sheep lung endothelial cell cDNA library. The gene, termed sp55, encodes a 495-amino acid polypeptide. COS-7 cells transfected with a vector containing sp55 express the SP55 protein-bound CM101 in a concentration-dependent manner. Stably transfected CHO cells also bound CM101. The corresponding human gene, hp59, was isolated from a human fetal lung cDNA library and had a predicted identity to SP55 of 86% over 495 amino acids. HP59 protein was shown by immunohistochemistry to be present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. The hp59 gene and/or the HP59 protein was not expressed in a variety of normal tissues, but was significantly expressed in human fetal lung, consistent with the pathophysiology of Group B streptococcus infections in neonates. Mice immunized with HP59 and SP55 peptides showed significant attenuation of tumor growth. Immunization effectively inhibited both the tumor angiogenesis and vasculogenesis processes, as evidenced by lack of both HP59- and CD34-positive vessels. These results and the immunohistochemistry data suggest a therapeutic potential for the CM101 target protein HP59 both as a drug target and as a vaccine against pathoangiogenesis.
抗血管药物CM101的I期研究。
DOI：
--
发表时间：
1997
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research.
影响因子：
--
作者：
DeVore,RF;Hellerqvist,CG;Wakefield,GB;Wamil,BD;Thurman,GB;Minton,PA;Sundell,HW;Yan,HP;Carter,CE;Wang,YF;York,GE;Zhang,MH;Johnson,DH
通讯作者：
Johnson,DH
使用改良的集落提升选择程序从杂交瘤细胞系 T84.66 生产单链抗 CEA 抗体，以检测抗原阳性 ScFv 细菌克隆。
影响因子：
--
作者：
Rodenburg,CM;Mernaugh,R;Bilbao,G;Khazaeli,MB
通讯作者：
Khazaeli,MB