title: A novel anti-Cyr61 antibody inhibits breast cancer growth and metastasis in vivo.
abstract: Cysteine-rich protein 61(CCN1/Cyr61) has been implicated as an important mediator in proliferation and metastasis of breast cancer, which indicated that blockage of Cyr61 might be a potent target for breast cancer treatment. However, the antitumor effect of anti-Cyr61 antibodies on breast cancer in vivo has not been reported so far. In this study, we reported the effect and likely mechanism of generated anti-human Cyr61 monoclonal antibodies (mAb) on Cyr61 high expression line MDA-MB-231, known as a highly malignant and invasive human breast cancer cell line, at aspects of proliferation and migration in vitro and in vivo. We found the mAb, denoted as 093G9, revealed inhibitory effects on MDA-MB-231 cell proliferation, migration, and invasion through downregulation of both AKT and ERK phosphorylation in vitro compared with its isotype control. 093G9 also showed significant efficacy on suppressing primary tumor growth and spontaneous lymph node metastasis in in vivo mouse model. The specific epitope recognized by 093G9 was identified to be (140)LPNLGCP(146), adjacent to the VWC domain of Cyr61 by Ph.D.-C7C phage library display system. Our study provides direct evidence that Cyr61 can be a potent therapeutic target for patients who bear high Cyr61 expression breast cancer. Furthermore, the mAb, 093G9 developed in our laboratory, has shown a promising therapeutic characteristic in breast cancer.
authors: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jinpiao
authors: J
authors: Lin
authors: Rongfen
authors: R
authors: Huo
authors: Li
authors: L
authors: Wang
authors: Zhou
authors: Z
authors: Zhou
authors: Yue
authors: Y
authors: Sun
authors: Baihua
authors: B
authors: Shen
authors: Rongfang
authors: R
authors: Wang
authors: Ningli
authors: N
authors: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D055515:Cysteine-Rich Protein 61 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D000939:Epitopes / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D055515:Cysteine-Rich Protein 61; D000939:Epitopes; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases