Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis

Miyazaki, Hiroshi; Patel, Vyomesh; Wang, Huixin; Edmunds, Ryan K.; Gutkind, J. Silvio; Yeudall, W. Andrew

doi:10.1158/0008-5472.can-05-4398

Cited by 100 publications

(97 citation statements)

References 34 publications

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“…Generation of Cell LinesThat Stably ExpressVimentin shRNA HN12 cells containing vimentin shRNA (shVim) or nontargeting control (NTC) plasmids were prepared essentially as described (16). Cells were cultured to 60% confluency and then transfected with 3 Ag plasmid DNA using TransIT Keratinocyte Reagent (Mirus Bio).…”

Section: Methodsmentioning

confidence: 99%

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Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Paccione

Miyazaki

Patel

et al. 2008

Molecular Cancer Therapeutics

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At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-B. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-B both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoterreporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness. [Mol Cancer Ther 2008;7(9):2894 -903]

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Section: Methodsmentioning

confidence: 99%

“…Quantitative Real-time PCR Quantitative real-time PCR (qRT-PCR) was done using an ABI 7500 Fast system (Applied Biosystems) and a SYBR Green-based procedure as described previously (16). Oligonucleotide pairs for use as PCR primers (Supplementary Table S1) 7 were designed using the Primerbank Webbased database (17).…”

Section: Methodsmentioning

confidence: 99%

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Paccione

Miyazaki

Patel

et al. 2008

Molecular Cancer Therapeutics

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“…Microarray analysis for gene expression profiling in OSCC identified gene signatures that include chemokine (CXC motif) ligand-13 (CXCL13) that is implicated in OSCC development and progression (5). Recent evidence indicated that down-regulation of CXCL5 expression inhibits head and neck squamous cell carcinoma development and invasion (15). Therefore, we examined the potential of CXCL13 to modulate RANKL expression in OSCC cells.…”

Section: Cxcl13 Stimulates Rankl Expression In Oscc Cellsmentioning

confidence: 99%

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Sambandam

Griffin

Sundaram

et al. 2009

Molecular Cancer Research

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Oral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion/ osteolysis. The chemokine ligand, CXCL13, has been identified as a prognostic marker for OSCC development and progression. Here in, we show that recombinant hCXCL13 treatment of OSCC cells stimulates (5-fold) RANK ligand (RANKL), a critical bone resorbing osteoclastogenic factor expression. Anti-CXCR5 chemokine receptor antibody abrogates CXCL13-induced RANKL expression in these cells. Also, CXCL13 stimulated (3.0-fold) hRANKL gene promoter activity in SCC14a cells. SuperArray screening for transcription factors by real-time RT-PCR identified significant increase in the levels of c-Jun and NFATc3 mRNA expression in CXCL13-stimulated OSCC cells. CXCL13 treatment significantly increased (3.5-fold) phospho-c-Jun levels in these cells and a c-Jun-NH 2 -kinase inhibitor abolished CXCL13-stimulated RANKL expression. Furthermore, we show that CXCL13 stimulation induced nuclear translocation of NFATc3 in OSCC cells. Chromatinimmune precipitation assay confirmed NFATc3 binding to the RANKL promoter region. We also show that overexpression of NFATc3 stimulates RANKL expression/ promoter activity and that siRNA suppression of NFATc3 abolished CXCL13-stimulated RANKL expression. Thus, our results suggest that NFATc3 is a downstream target of the CXCL13/CXCR5 axis to stimulate RANKL expression in OSCC cells and implicates CXCL13 as a potential therapeutic target to prevent OSCC bone invasion/

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“…Data suggest that CXCL5 enhances tumor development by stimulating proliferation, cell motility and invasion [107] as knockdown of CXCL5 by siRNA completely inhibited tumorigenicity in a mouse xenograft model.…”

Section: Oral Cavitymentioning

confidence: 99%

“…However, it is not yet confirmed if this observation is a consequence of secondary change as a result of gastric cancer progression, or whether it is one of the primary molecular events leading to tumor development. As CXCL5 is linked to tumor development in other organs [77,107,138] , further confirmation is needed through the use of in vitro and in vivo model systems in the future. Yanagie et al [139] performed a comparative analysis of differential gene expression related to chemokines/chemokine receptors and cytokines in established gastric cancer cell lines using a cDNA microarray approach.…”

Section: Stomachmentioning

confidence: 99%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis

Cited by 100 publications

References 34 publications

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Chemokines, chemokine receptors and the gastrointestinal system

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