Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

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.

Tumor intrinsic immunity related proteins may be novel tumor suppressors in some types of cancer

“…Therefore, the role of CEACAM1 in cancer cells may be different from its role of inhibiting anti-tumor immune responses in T cells. Our findings were supported by the previous research pointing to the tumor suppressor role of CEACAM1 47–55 . A most recent study suggested that CEACAM1 overexpression significantly suppressed cancer cell proliferation, induced cancer cell apoptosis, and inhibited cancer cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9 47 .…”

MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study

“…Previous study has suggested SMAD7 can induce growth and inhibit apoptosis in colon adenocarcinoma cells and acts as a tumor promoter [35], indicating that miR-581-mediated apoptosis might be SMAD7/TGFβ-pathway-independent. Moreover, in the results of miR-581 target genes, TNFSF10 [36,37], HMGA2 [38], CEACAM1 [39,40], and mTOR [41] have been reported to be involved in proliferation and apoptosis in a number of cancers. There is a strong possibility that miR-581 regulates CRC proliferation and apoptosis by targeting these genes.…”

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets

“…Due to unique sialofucosylated glycoforms within its GPI anchor, CEA was found to bind to L-selectin and E-selectin, therefore mediating cell adhesion. CEA-CAM 1 is tumor suppressing through decreasing cell proliferation and metastasis, while CEA-CAM-5 is tumor promoting through inhibiting colon cell differentiation, anoikis and apoptosis (65,66). This is attributed to CEA-CAM-5 co-localization and subsequent activation of a5ß1 integrin signal transduction, triggering PI3K/AKT activity (67).…”