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Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.

ABSTRACT: To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo.We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown.Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction.Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.

SUBMITTER: Xu Y

PROVIDER: S-EPMC3386327 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.

Xu Yu Y Zhang Jin J Liu Qi-Sheng QS Dong Wei-Guo WG

World journal of gastroenterology 20120601 24

<h4>Aim</h4>To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo.<h4>Methods</h4>We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft ...[more]

PMID: 22791949

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Project description:Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)?, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.

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Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.

Publications

Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.

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