Cancer Biomarkers - Volume 21, issue 4

Authors: Liu, Yuan | Men, Changping | Xu, Yingmin | Zhao, Kai | Luo, Lei | Dong, Dahai | Yu, Qinchao

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Clusterin promotes cell proliferation, motility and invasiveness in human renal cell carcinoma (RCC) cells but the underlying molecular mechanisms of this action are largely unknown. The aim of this study was to investigate the effects of clusterin on cancer cell growth, invasion and S100A4 expression and to determine the effects of clusterin on in vitro cell proliferation and migration and in vivo tumour growth in RCC cells. METHODS: We have established stable transfectants of highly invasive Caki-1 human RCC cells with expression of clusterin shRNA targeting clusterin (Caki-1/clusterin shRNA). We also …established stable transfectants of 786-O human RCC cells with expression of clusterin cDNA plaismid (786-O/clusterin cDNA). Clusterin and S100A4 expression was detected by reverse transcription (RT) PCR and western blot assay; Caki-1/clusterin shRNA and 786-O/clusterin cDNA clones were subjected to in vitro -invasion assays. Cell viability and cell growth was assessed in MTT and clonogenic assay. Specific small interfering RNA was employed to down-regulate S100A4. The expression plasmid for S100A4 (pCMV-S100A4) was used to upregulate S100A4. Caki-1/clusterin shRNA clones were injected subcutaneously in nude mice to determine tumour growth and cancer cell invasiveness in vivo . Xenograft tumour tissues were assessed by immunohistochemistry and frozen tissues were used for the detection of S100A4 and clusterin. RESULTS: Overexpression of clusterin increased cell invasiveness; and targeting clusterin reduced cell invasiveness in vitro . This increase in cell invasiveness was mediated by S100A4. Targeting clusterin decreased cell proliferation and down-regulated cellular S100A4 levels in Caki-1 cells; Overexpression of clusterin increased cell proliferation and up-regulated cellular S100A4 levels in 786-O cells; Stable Caki-1/clusterin shRNA transfectants produced smaller xenograft tumours containing reduced S100A4 protein levels in vivo . Stable 786-O/clusterin cDNA transfectants produced larger xenograft tumours containing increased S100A4 protein levels in vivo . CONCLUSION: Our results indicate that clusterin promotes growth and invasion in RCC cells in vitro and in vivo through upregulation of S100A4; And targeting clusterin confers growth inhibitory and anti-invasive properties in RCC cells in vitro and in vivo through a down-regulation of S100A4. These findings provide the rationale for future oncostatic strategies aimed at suppressing clusterin-mediated signal transduction pathways as a novel therapeutic approach in human RCC. Show more

Keywords: Renal cell carcinoma, invasion, growth, clusterin, S100a4

DOI: 10.3233/CBM-171018

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 915-923, 2018

Authors: Zhou, Qianping | Huang, Lanshan | Gu, Yongyao | Lu, Huiping | Feng, Zhenbo

Article Type: Research Article

Abstract: BACKGROUND: Molecular target therapy has become a hot spot in cancer treatment, finding effective targets for diffuse large B cell lymphoma (DLBCL) is an urgent problem. OBJECTIVE: To detect the expression level of C-C motif chemokine ligand 18 (CCL18) in DLBCL and clarify its potential role in the progression of DLBCL. METHODS: Gene expression datas of DLBCL were obtained from TCGA and GEO databases. The relationship between CCL18 and clinicopathologic information of DLBCL was assessed using meta-analysis method. Then we conducted bioinformatics analysis to uncover the biological function of CCL18 and its co-expression …genes. Immunohistochemistry was applied to detect expression of CCL18 in DLBCL and reactive hyperplasia lymphoid tissues. RESULTS: The expression of CCL18 in DLBCL was higher than negative control group. The levels of CCL18 were distinct in different molecular subtypes and ages, and patients with higher level of CCL18 had a shorter overall survival than those with lower level. CCL18 and its co-expression genes were enriched in biological function such as cell proliferation, migration, apoptotic, and correlated with NF-κ B, pathway in cancer, PI3K-AKT pathway. CONCLUSIONS: CCL18 was up-regulated in DLBCL and related to poor prognosis. CCL18 may act as a valuable target for diagnosis and treatment of DLBCL. Show more

Keywords: CCL18, DLBCL, meta-analysis, bioinformatics, immunohistochemistry

DOI: 10.3233/CBM-171097

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 925-934, 2018