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

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.

• Authors: Mingde Zang, Yunqiang Zhang, Baogui Zhang, Lei Hu, Jianfang Li, Zhiyuan Fan, Hexiao Wang, Liping Su, Zhenggang Zhu, Chen Li, Chao Yan, Qinlong Gu, Bingya Liu, Min Yan
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1852 Issue 5 Pg. 1020-8 (May 2015) ISSN: 0006-3002 [Print] Netherlands
• PMID: 25703140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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