Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis

Oncotarget. 2016 Aug 2;7(31):49972-49985. doi: 10.18632/oncotarget.10267.

Abstract

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.

Keywords: antibody; cancer; cell migration; gC1qR; lamellipodia.

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Carcinogenesis
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / immunology
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial Proteins / antagonists & inhibitors*
  • Mitochondrial Proteins / immunology
  • Mitochondrial Proteins / metabolism
  • Phosphorylation
  • Pseudopodia / drug effects*
  • Signal Transduction

Substances

  • Antibodies
  • C1QBP protein, human
  • Carrier Proteins
  • Mitochondrial Proteins