CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling

Biochim Biophys Acta. 2015 May;1852(5):1020-8. doi: 10.1016/j.bbadis.2015.02.005. Epub 2015 Feb 19.

Abstract

CEACAM6 is a member of glycosylphosphatidylinositol-linked immunoglobulin superfamily that is implicated in a variety of human cancers. In our previous study, we reported that CEACAM6 was overexpressed in gastric cancer tissues and promoted cancer metastasis. The purpose of this study is to determine the role of CEACAM6 in tumor angiogenesis and mimicry formation. We found that overexpressed CEACAM6 promoted tubule formation dependent on HUVEC cells and vasculogenic mimicry formation of gastric cancer cells; opposing results were achieved in CEACAM6-silenced groups. Moreover, we found that mosaic vessels formed by HUVEC cells and gastric cancer cells were observed in vitro by 3D-culture assay. Overexpressed CEACAM6 in gastric cancer cells promoted tumor growth, VEGF expression and vasculogenic mimicry structures formation in vivo. In accordance with these observations, we found that phosphorylation of FAK and phosphorylation of paxillin were up-regulated in CEACAM6-overexpressing gastric cancer cells, and FAK inhibitor Y15 could reduce tubule and vasculogenic mimicry formation. These findings suggest that CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry formation via FAK signaling in gastric cancer and CEACAM6 may be a new target for cancer anti-vascular treatment.

Keywords: Angiogenesis; CEACAM6; FAK; Gastric cancer; VM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Blood Vessels / drug effects
  • Blood Vessels / physiology
  • Blotting, Western
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Focal Adhesion Kinase 1 / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic / drug effects
  • Paxillin / metabolism
  • Phosphorylation / drug effects
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Transplantation, Heterologous

Substances

  • Antigens, CD
  • CEACAM6 protein, human
  • Cell Adhesion Molecules
  • Culture Media, Conditioned
  • GPI-Linked Proteins
  • Paxillin
  • Focal Adhesion Kinase 1
  • PTK2 protein, human