Kim Beom-Chan, Hwang Hyun-Jung, An Hyoung-Tae, Lee Hyun, Park Jun-Sub, Hong Jin, Ko Jesang, Kim Chungho, Lee Jae-Seon, Ko Young-Gyu
Tunneling Nanotube Research Center, Korea University, Seoul, 02841, Korea.
Division of Life Sciences, Korea University, Seoul, 02841, Korea.
Oncotarget. 2016 Aug 2;7(31):49972-49985. doi: 10.18632/oncotarget.10267.
We previously demonstrated that cell-surface gC1qR is a key regulator of lamellipodia formation and cancer metastasis. Here, we screened a monoclonal mouse antibody against gC1qR to prevent cell migration by neutralizing cell-surface gC1qR. The anti-gC1qR antibody prevented growth factor-stimulated lamellipodia formation, cell migration and focal adhesion kinase activation by inactivating receptor tyrosine kinases (RTKs) in various cancer cells such as A549, MDA-MB-231, MCF7 and HeLa cells. The antibody neutralization of cell-surface gC1qR also inhibited angiogenesis because the anti-gC1qR antibody prevented growth factor-stimulated RTK activation, lamellipodia formation, cell migration and tube formation in HUVEC. In addition, we found that A549 tumorigenesis was reduced in a xenograft mouse model by following the administration of the anti-gC1qR antibody. With these data, we can conclude that the antibody neutralization of cell-surface gC1qR could be a good therapeutic strategy for cancer treatment.
我们先前证明，细胞表面的gC1qR是板状伪足形成和癌症转移的关键调节因子。在此，我们筛选了一种针对gC1qR的单克隆小鼠抗体，通过中和细胞表面的gC1qR来阻止细胞迁移。抗gC1qR抗体通过使各种癌细胞（如A549、MDA-MB-231、MCF7和HeLa细胞）中的受体酪氨酸激酶（RTK）失活，从而阻止生长因子刺激的板状伪足形成、细胞迁移和粘着斑激酶激活。细胞表面gC1qR的抗体中和作用还抑制了血管生成，因为抗gC1qR抗体阻止了生长因子刺激的人脐静脉内皮细胞（HUVEC）中的RTK激活、板状伪足形成、细胞迁移和管腔形成。此外，我们发现，在异种移植小鼠模型中，给予抗gC1qR抗体后，A549肿瘤发生减少。基于这些数据，我们可以得出结论，细胞表面gC1qR的抗体中和作用可能是一种很好的癌症治疗策略。
