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Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors.

ABSTRACT: Cell adhesion molecule 1 (CADM1) regulates cell-cell adhesion and an altered expression level is associated with tumorigenesis and progression. The present study assessed CADM1 expression level in 84 bladder tissues to investigate the association with clinicopathological parameters from bladder cancer patients and then investigated the effects of CADM1 overexpression on T24 bladder cancer cells in vitro. The results demonstrated that expression level of CADM1 protein was significantly reduced in bladder cancer tissues (0.26±0.14) compared with in normal bladder mucosa (0.69±0.092; P<0.01), and methylation of CADM1 promoter was responsible for silencing of CADM1 protein expression and significantly associated with tumor size, recurrence, pathology classification and clinical stage (P<0.05). Overexpression of CADM1 protein inhibited tumor cell proliferation, reduced tumor cell invasion capacity and induced tumor cell apoptosis in vitro. At the gene level, CADM1 expression level upregulated caspase-3 activity and expression of Bax and p27 protein and downregulated levels of B cell lymphoma-2, cyclinD1, cyclinE1 and cyclin dependent kinase 2 proteins. Furthermore, overexpression of CADM1 regulated the expression level of epithelial to mesenchymal transition markers, including increased expression level of E-cadherin and ?-catenin, whereas it decreased the levels of Vimentin. The present study demonstrated that lost expression of CADM1 protein may exert an essential role in the development and progression of bladder cancer and suggested that CADM1 may be a novel molecular target for the control of this disease in clinical practice.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6350208 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors.

Chen Yegang Y Liu Li L Guo Zhanjun Z Wang Yi Y Yang Yongjiao Y Liu Xiaoqiang X

Oncology letters 20181218 2

Cell adhesion molecule 1 (CADM1) regulates cell-cell adhesion and an altered expression level is associated with tumorigenesis and progression. The present study assessed CADM1 expression level in 84 bladder tissues to investigate the association with clinicopathological parameters from bladder cancer patients and then investigated the effects of CADM1 overexpression on T24 bladder cancer cells <i>in vitro</i>. The results demonstrated that expression level of CADM1 protein was significantly red ...[more]

PMID: 30719104

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Project description:BackgroundLutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. This study was performed to investigate the role and downstream signaling pathway of Lu/BCAM in human bladder tumorigenesis.MethodsFive human bladder cancer (E6, RT4, TSGH8301, TCCSUP and J82), one stable mouse fibroblast cell line (NIH-Lu) expressing Lu/BCAM transgene and sixty human uroepithelial carcinoma specimens were analyzed by real-time PCR, immunohistochemistry (IHC), immunofluorescence (IFA) staining, Western blotting and promoter luciferase assay for Lu/BCAM, respectively. The tumorigenicity of Lu/BCAM was demonstrated by focus formation, colony-forming ability, tumour formation, cell adhesion and migration.ResultsH-ras V12 was revealed to up-regulate Lu/BCAM at both transcriptional and translation levels. Lu/BCAM expression was detected on the membrane of primary human bladder cancer cells. Over-expression of Lu/BCAM in NIH-Lu stable cells increased focus number, colony formation and cell adhesion accompanied with F-actin rearrangement and decreased cell migration compared with parental NIH3T3 fibroblasts. In the presence of laminin ligand, Lu/BCAM overexpression further suppressed cell migration accompanied with increased cell adhesion. We further revealed that laminin-Lu/BCAM-induced cell adhesion and F-actin rearrangement were through increased Erk phosphorylation with an increase of RhoA and a decrease of Rac1 activity. Similarly, high Lu/BCAM expression was detected in the tumors of human renal pelvis, ureter and bladder, and was significantly associated with advanced tumor stage (p = 0.02). Patients with high Lu/BCAM expression showed a trend toward larger tumor size (p = 0.07) and lower disease-specific survival (p = 0.08), although not reaching statistical significance.ConclusionThis is the first report showing that Lu/BCAM, in the presence of its ligand laminin, is oncogenic in human urothelial cancers and may have potential as a novel therapeutic target.

Project description:BackgroundThe study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers.MethodsInhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins.ResultsBoth tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin.ConclusionsTanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

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Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors.

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Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors.

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