Abstract
CEACAM1 is associated with malignant potential of various cancers. The current study aims to clarify the association between carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression and malignant potential of gastric cancer and to address whether CEACAM1 cytoplasmic domain isoform balance modulates the properties of gastric cancer cells. Immunohistochemical analyses for CEACAM1 were performed in 235 patients with gastric cancer who underwent surgery. Risk factors for overall survival and peritoneal metastasis were calculated based on CEACAM1 expression in the gastric cancer tissue. Patients with CEACAM1 long (CEACAM1-L) or short (CEACAM1-S) cytoplasmic isoform dominance were compared with patients with null CEACAM1 expression in terms of overall survival. CEACAM1 transfected or knockdown gastric cancer cell line, NUGC3 and MKN7 cells, were examined by invasion assay and three dimensional (3D) culture, in order to clarify whether CEACAM1 modulate invasion, lumen formation and tumor growth of gastric cancer cells. Multivariate analysis demonstrated that gastric cancer without CEACAM1 is an independent prognostic factor and a risk factor for peritoneal dissemination. Patients with CEACAM1-S dominance had better prognosis than those with CEACAM1-L. CEACAM1-4L overexpression induced less invasion, more lumen formation, and less tumor growth of NUGC3 cells. CEACAM1-4S overexpression had less invasion and more lumen formations, but not less tumor growth. Knockdown of CEACAM1 expression had less invasion, but not less lumen formations of MKN7 cells. Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer. Expression of CEACAM1 in gastric cancer cells modulates invasiveness, lumen formation, and tumor growth.
Highlights
Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) belonging to the immunoglobulin superfamily and the carcinoembryonic antigen (CEA) family is a transmembrane protein and cell–cell adhesion molecule
In colorectal cancer and hepatocellular carcinoma (HCC), we have reported that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is associated with invasion, metastasis and poor prognosis[7,8,9]
The Kaplan-Meier method for the overall survival analysis showed that non CEACAM1-expression group was significantly associated with a shorter survival time (Fig. 2)
Summary
Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) belonging to the immunoglobulin superfamily and the carcinoembryonic antigen (CEA) family is a transmembrane protein and cell–cell adhesion molecule. In colorectal cancer and hepatocellular carcinoma (HCC), we have reported that CEACAM1 is associated with invasion, metastasis and poor prognosis[7,8,9]. CEACAM1 long cytoplasmic domain isoform (CEACAM1-4L) promotes colorectal cancer cell invasion and migration[7]. There is a possibility that similar changes, such as colorectal cancer and HCC, may occur by expression and cytoplasmic domain isoform balance of CEACAM1. We examined implications of CEACAM1 cytoplasmic domain isoform balance for patients with gastric cancer. We explore the notion that enhanced CEACAM1 cytoplasmic isoform (CEACAM1-4L or CEACAM1-4S) modulates malignant properties such as invasion, lumen formation and tumor growth of gastric cell line
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
