Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4) is specifically expressed in medullary thyroid carcinoma cells

Abstract

Carcinoembryonic antigen (CEA), an oncofetal cell surface glycoprotein, has been widely used as a human tumor marker due to its high expression in tumors and secretion to serum. It belongs to the immunoglobulin superfamily named CEA-related cell adhesion molecule (CEACAM) family. Members of this family are detected in various cancers and have been shown to be involved in cancer growth and invasion. In this study, we examined the mRNA expression profiles of CEACAM family members including CEACAM1, CEACAM3, CEACAM4, CEACAM5 (CEA), CEACAM6, CEACAM7, and CEACAM8 in various tumor cell lines. Our screening data indicated that the mRNA expression patterns of CEACAMs in TT cells, which are derived from medullary thyroid carcinoma (MTC), were distinct from other tumor cell lines. Additionally, CEACAM4 was only expressed in TT cells, in which two novel splice variants of CEACAM4 were expressed. These findings suggested that production of CEA and CEA-related molecules in MTC may be distinct from other tumor-based production of those molecules and that the specific expression of CEACAM4 would make possible to differentiate between MTC and other CEA-producing tumors.Carcinoembryonic antigen (CEA) is the product of the CEA-related cell adhesion molecule 5 (CEACAM5) gene and is produced in a high percentage of human tumors, including 90% of gastrointestinal cancers, 70% of lung cancers, and 50% of breast cancers (22). Because of its high secretion into the serum, CEA has been widely used as a serum tumor marker; currently, CEA analysis is used to monitor the progression of several types of cancer following surgery. CEA belongs to the CEACAM subfamily of the immunoglobulin (Ig) superfamily. The members of this family have been identified as CEA crossreacting antigens and have been found in tumor sites with elevated CEA-like activity. Moreover, CEACAMs are also produced in various tumors, and recent studies have suggested that multivariable analysis of CEACAMs may improve the clinical utility of CEA as a tumor maker (6, 24). For example, Simeone et al. reported that CEACAM1 may be used to enhance the efficacy of other known pancreatic tumor markers and may have better sensitivity and specificity than CA19-9 and CEA for the detection of pancreatic carcinoma (20). In addition, using those biomarkers in combination with CEACAM1 may represent a novel method for the diagnosis of early-stage pancreatic carcinoma. In this study, we analyzed the mRNA expression profiles of CEACAM family members in colonic, gastric, pancreatic, lung, breast, and thyroid cancer cell lines. Our data demonstrated that a medullary thyroid carcinoma (MTC)-derived cell line exhibited unique CEACAM expression patterns, with CEACAM4 specifically expressed in TT cells.

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

“…Two PPIs were detected for the orphan granulocyte receptor CEACAM4: (1) vascular endothelial growth factor receptor 3 (VEGFR3), and (2) programmed cell death 1 ligand 2 (PD-L2). CEACAM4 is a member of the carcinoembryonic antigen-related cell adhesion molecule subfamily expressed in the immune system, epithelial and endothelial cells, and brain ( Wakabayashi-Nakao et al., 2014 ; Zinn and Özkan, 2017 ). In the immune system, CEACAMs play roles in immunity and development.…”

Key sunitinib‐related biomarkers for renal cell carcinoma

“…Additionally, CEACAM4 which is expressed in primary human granulocytes was reported to be involved in systemic inflammation 53–55 . Moreover, CEACAM4 has been validated to be associated with esophageal squamous cell carcinoma 56 and medullary thyroid carcinoma 51 . All of these indicated CEACAM4 was highly related to both immune and tumor.…”

“…CEACAM4 is a member of carcinoembryonic antigen‐related cell adhesion molecule (CEACAM) family, which is expressed highly in tumors and secreted in serum, and has been widely used as human tumor markers. The CEACAM family is also reported to refer to tumor growth and aggression 51,52 . Additionally, CEACAM4 which is expressed in primary human granulocytes was reported to be involved in systemic inflammation 53–55 .…”

Be(a)ware of Leukocytosis in Papillary Thyroid Cancer

“…Moreover, tumor cells were positive for CEA with elevated CEA serum levels. CEA is produced as an expression of CEA-related cell adhesion molecule 5 gene and is found in 90% of gastrointestinal cancers, 70% of lung cancers, and 50% of breast cancers [ 25 ]. Elevated levels may also be seen in ovarian cancer, appendix, mucinous cystadenoma, and medullary thyroid carcinoma.…”