Jinge Xu1,2,3, Bin Liu1,2, Shoubao Ma1,2,4, Jubin Zhang1, Yuhan Ji1, Liangjing Xu1, Mingqing Zhu1, Suning Chen1, Xiaojin Wu1,2,4, Depei Wu1,2,4. 1. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. 2. Institute of Blood and Marrow Transplantation, Suzhou, China. 3. The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. 4. Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Abstract
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 pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV-FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. RESULTS: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. CONCLUSION: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.
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 pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV-FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. RESULTS:CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. CONCLUSION: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.
Authors: Ondrej Venglar; Julio Rodriguez Bago; Benjamin Motais; Roman Hajek; Tomas Jelinek Journal: Front Immunol Date: 2022-01-11 Impact factor: 7.561