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Sophie Mißbach, Denis Aleksic, Lisa Blaschke, Timm Hassemer, Kyung Jin Lee, Martin Mansfeld, Jana Hänske, Johannes Handler, Robert Kammerer
BACKGROUND: The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified...
March 15, 2018: BMC Evolutionary Biology
Jinge Xu, Bin Liu, Shoubao Ma, Jubin Zhang, Yuhan Ji, Liangjing Xu, Mingqing Zhu, Suning Chen, Xiaojin Wu, Depei Wu
BACKGROUND/AIMS: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. METHODS: pEGFP-N1-CEACAM1 and pcDNA3...
February 21, 2018: Cellular Physiology and Biochemistry
Jinhu Li, Xiaodong Liu, Yijun Duan, Hongqin Wang, Wen Su, Yazhou Wang, Guotao Zhuang, Yimin Fan
Glioma, the most prevalent primary tumor of the central nervous system, is known to evade immune surveillance and escape immune attacks by inducing immunosuppression. The homophilic interactions of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) serve a critical function in immunoregulation. In the present study, the expression levels of CEACAM1 in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes (TILs) from patients with gliomas were assessed. Furthermore, associations between CEACAM1 expression and multiple clinicopathological characteristics in patients with gliomas were analyzed...
March 2018: Oncology Letters
Kenric Tam, David W Schoppy, June Ho Shin, Joshua K Tay, Uriel Moreno-Nieves, David C Mundy, John B Sunwoo
Objective In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged as a fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Understanding the mechanisms by which HNSCC evades immune-mediated control will aid in the development of new therapies to augment an antitumor immune response. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on malignant cells and lymphocytes such as natural killer (NK) cells...
February 1, 2018: Otolaryngology—Head and Neck Surgery
Qi Xie, Xiaocui Chen, Yinghua Xu, Jing Liang, Fufang Wang, Ju Liu
Tube formation is one of the fundamental events required by angiogenesis and lymphangiogenesis. To date, there is little knowledge on the effects of hypoxia on tube formation of human dermal lymphatic endothelial cells (HDLECs). In this study, we found that tube formation of HDLECs was inhibited under hypoxic condition with decreased expressions of VEGF-D, CEACAM1 and Prox1 genes. However, hypoxia-induced inhibition of tube formation of HDLECs was reversed by conditional media from hypoxic tumor cells. After knockdown of CEACAM1 by siRNA transfection, tube formation of HDLECs was increased with elevated Prox1 expression, suggesting that CEACAM1 downregulates Prox1 and plays an inhibitory role in tube formation of HDLECs...
February 7, 2018: Cellular Signalling
Hilda E Ghadieh, Harrison T Muturi, Lucia Russo, Christopher C Marino, Simona S Ghanem, Saja S Khuder, Julie C Hanna, Sukanta Jash, Vishwajeet Puri, Garrett Heinrich, Cara Gatto-Weis, Kevin Y Lee, Sonia M Najjar
Exenatide, a glucagon-like peptide-1 receptor agonist, induces insulin secretion. Its role in insulin clearance has not been adequately examined. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance to maintain insulin sensitivity. Feeding C57BL/6J mice a high-fat diet down-regulates hepatic Ceacam1 transcription to cause hyperinsulinemia, insulin resistance, and hepatic steatosis, as in Ceacam1 null mice (Cc1-/- ). Thus, we tested whether exenatide regulates Ceacam1 expression in high-fat diet-fed mice and whether this contributes to its insulin sensitizing effect...
January 2018: Hepatology Communications
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Alexander M Wisniewski, Eric E Morgan, Syed S Quadri, Gavin P Landesberg, Helmy M Siragy, Guillermo Vazquez, Rosario Scalia, Rajesh Gupta, Sonia M Najjar
OBJECTIVE: Mice with global null mutation of Ceacam1 (Cc1-/-), display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1-/-liver+ mice. The current study examined whether Cc1-/- male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction...
January 26, 2018: Molecular Metabolism
Andrea Kristina Horst, Claudia Wegscheid, Christoph Schaefers, Birgit Schiller, Katrin Neumann, Sebastian Lunemann, Annika E Langeneckert, Karl J Oldhafer, Christina Weiler-Normann, Karl S Lang, Bernhard B Singer, Marcus Altfeld, Linda Diehl, Gisa Tiegs
A dysbalance between effector T cells (Tconv) and regulatory T cells (Tregs) and impaired Tregs function can cause autoimmune liver disease. Therefore, it is important to identify molecular mechanisms that control Treg homeostasis. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is an immune co-receptor with dichotomous roles in T cell regulation: its short isoform (CEACAM1S) can activate T cells and induce Tregs, whereas its long isoform (CEACAM1L) containing two intracellular immune receptor tyrosine-based inhibitory motifs (ITIMs), can inhibit activated T cell function...
January 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Robert J Torphy, Richard D Schulick, Yuwen Zhu
Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors...
December 6, 2017: International Journal of Molecular Sciences
Shunsuke Yamaguchi, Shozo Yokoyama, Masaki Ueno, Shinya Hayami, Yasuyuki Mitani, Akihiro Takeuchi, John E Shively, Hiroki Yamaue
BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is re-expressed at the invasion front of colorectal cancer. CEACAM1 expression at metastatic sites remains to be investigated. The current study aims to clarify the association between CEACAM1 expression and recurrence after hepatectomy of colorectal liver metastasis and to address whether CEACAM1 induces tumor-initiating properties needed for growth at metastatic sites. METHODS: Immunohistochemical analyses for CEACAM1 were performed in 67 patients with liver metastasis of colorectal cancer who had undergone curative hepatectomy...
December 2017: Journal of Surgical Research
Won Kyu Kim, Yujin Kwon, Minhee Park, Seongju Yun, Ja-Young Kwon, Hoguen Kim
High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed...
November 2017: BMB Reports
Ashish Goyal, Evgenij Fiškin, Tony Gutschner, Maria Polycarpou-Schwarz, Matthias Groß, Julia Neugebauer, Minakshi Gandhi, Maiwen Caudron-Herger, Vladimir Benes, Sven Diederichs
Long non-coding RNAs (lncRNAs) have been proven to play important roles in diverse cellular processes including the DNA damage response. Nearly 40% of annotated lncRNAs are transcribed in antisense direction to other genes and have often been implicated in their regulation via transcript- or transcription-dependent mechanisms. However, it remains unclear whether inverse correlation of gene expression would generally point toward a regulatory interaction between the genes. Here, we profiled lncRNA and mRNA expression in lung and liver cancer cells after exposure to DNA damage...
December 1, 2017: Nucleic Acids Research
C-S Mao, H Yin, H-B Ning, Z Peng, K Li, G-Q Ding
OBJECTIVE: Hepatitis B virus X protein (HBx), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), are related to HBV associated hepatocellular carcinoma (HCC). This study recruited HCC patients and employed the SMMC-7721 and L02 liver cell lines, to analyze the expression levels of HBx, VEGF and CEACAM1 in liver cancer and their correlation with the cancer prognosis. PATIENTS AND METHODS: HBV-related HCC patients were recruited from our hospital...
October 2017: European Review for Medical and Pharmacological Sciences
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Simona S Ghanem, Thomas A Bowman, Hye Lim Noh, Sezin Dagdeviren, Godwin Y Dogbey, Jason K Kim, Garrett Heinrich, Sonia M Najjar
AIMS/HYPOTHESIS: The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Mice with global null mutation (Cc1 (-/-)) or with liver-specific inactivation (L-SACC1) of Cc1 (also known as Ceacam1) gene display hyperinsulinaemia resulting from impaired insulin clearance, insulin resistance, steatohepatitis and obesity. Because increased lipolysis contributes to the metabolic phenotype caused by transgenic inactivation of CEACAM1 in the liver, we aimed to further investigate the primary role of hepatic CEACAM1-dependent insulin clearance in insulin and lipid homeostasis...
December 2017: Diabetologia
Oriana Simonetti, Guendalina Lucarini, Corrado Rubini, Antonio Zizzi, Simone Domenico Aspriello, Roberto Di Primio, Anna Maria Offidani
Squamous cell carcinoma of the oral cavity represents the sixth most common cancer worldwide and it is often preceded by pre-neoplastic lesions. Sometimes it is still difficult for pathologists to make objective differential diagnoses only on histological characteristics. Tumorigenesis is accompanied by altered expression of cell adhesion molecules, like carcinoembryonic antigen cell adhesion molecule (CEACAM)1. We wanted to investigative CEACAM1 in oral dysplastic lesions, carcinoma in situ (CIS) and oral squamous cell carcinoma (OSCC)...
September 8, 2017: Medical Molecular Morphology
Matthew Dankner, Scott D Gray-Owen, Yu-Hwa Huang, Richard S Blumberg, Nicole Beauchemin
CEACAM1 is an extensively studied cell surface molecule with established functions in multiple cancer types, as well as in various compartments of the immune system. Due to its multi-faceted role as a recently appreciated immune checkpoint inhibitor and tumor marker, CEACAM1 is an attractive target for cancer immunotherapy. Herein, we highlight CEACAM1's function in various immune compartments and cancer types, including in the context of metastatic disease. This review outlines CEACAM1's role as a therapeutic target for cancer treatment in light of these properties...
2017: Oncoimmunology
Jennifer Chean, Charng-Jui Chen, John E Shively
The loss of expression of a single gene can revert normal tissue to a malignant phenotype. For example, while normal breast has high lumenal expression of CEACAM1, the majority of breast cancers exhibit the early loss of this gene with the concurrent loss of their lumenal phenotype. MCF7 cells that lack CEACAM1 expression and fail to form lumena in 3D culture, regain the normal phenotype when transfected with CEACAM1. In order to probe the mechanism of this gain of function, we treated these cells with the clinically relevant Jak2 inhibitor TG101348 (TG), expecting that disruption of the prolactin receptor signaling pathway would interfere with the positive effects of transfection of MCF7 cells with CEACAM1...
October 1, 2017: Experimental Cell Research
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Muqing Zhou, Zhiming Jin, Yiwen Liu, Yiqing He, Yan Du, Cuixia Yang, Yingzhi Wang, Jiajie Hu, Lian Cui, Feng Gao, Manlin Cao
Serum carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is dysregulated in various malignant tumors and has been associated with tumor progression. However, the expression and regulatory mechanisms of serum CEACAM1 in gastrointestinal cancer are still unclear. The expression ratio of the CEACAM1-L and CEACAM1-S isoforms has seldom been investigated in gastrointestinal cancer. In this study, we intended to explore the expression and diagnostic value of CEACAM1 in gastrointestinal cancer. Serum CEACAM1 levels were measured by enzyme-linked immunosorbent assay...
August 1, 2017: Acta Biochimica et Biophysica Sinica
Pawel Mach, Alexandra Gellhaus, Sebastian Prager, Tom Moore, Gunther Wennemuth, Rainer Kimmig, Angela Köninger, Bernhard B Singer
PROBLEM: CEACAM1 and CEACAM6 belong to the carcinoembryonic antigen (CEA) family and may play an immune-modulatory role during pregnancy. The aim of the study was to determine the blood serum levels of soluble CEACAM1 and CEACAM6 over the course of pregnancy and postpartum. METHOD OF STUDY: CEACAM1 and CEACAM6 levels were determined with customized in-house Sandwich-enzyme-linked immunosorbent assay (ELISA) systems. The study population (n=125) was divided into four groups according to the pregnancy trimester and postpartum...
June 8, 2017: American Journal of Reproductive Immunology: AJRI
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