Molecular mediators of metastasis in head and neck squamous cell carcinoma

Howell, Gina M.; Grandis, Jennifer R.

doi:10.1002/hed.20222

Cited by 67 publications

(62 citation statements)

References 56 publications

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“…3 Metastasis is a dynamic process in which the interplay of tumor cell, host, and tissue microenvironment factors play a critical role, particularly in the signaling pathways that regulate homotypic and heterotypic cell-cell and cellmatrix interactions. 4 In advanced cancers in general, the final stages of tumor differentiation and progression are characterized by the invasion of tumor cells into the surrounding tissue and their dissemination to form metastases in distant organs. 5 Conceptually, the metastatic "cascade" is multifactorial and comprises the loss of cancer cell adherence at the primary site, cell motility, proteolysis of the extracellular matrix (ECM) and basement membrane, invasion of local stroma, entry of vascular and lymphatic vessels (intravasion), extravasion, recolonization, and expansion into distant sites.…”

Section: Introductionmentioning

confidence: 99%

“…5 Conceptually, the metastatic "cascade" is multifactorial and comprises the loss of cancer cell adherence at the primary site, cell motility, proteolysis of the extracellular matrix (ECM) and basement membrane, invasion of local stroma, entry of vascular and lymphatic vessels (intravasion), extravasion, recolonization, and expansion into distant sites. [4][5][6] During this process, epithelial-mesenchymal transition (EMT) is established as a critical mechanism by which epithelial cells acquire sufficient plasticity and motile properties to become invasive. In addition, increasing evidence supports a link between EMT in the selection of cancer cell variants with stem cell properties and chemotherapy resistance.…”

Section: Introductionmentioning

confidence: 99%

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TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Silva

Alaoui‐Jamali

Soares

et al. 2013

Cancer

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BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis. METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment. RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo. CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC. Cancer 2014;120:352-62.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Silva

Alaoui‐Jamali

Soares

et al. 2013

Cancer

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“…It is generally accepted that the high mortality and poor prognosis associated with HNSCC is best predicted by the presence of cervical lymph node metastases, a common and adverse event in patients with HNSCC, reducing survival by approximately 50% [35,36]. To evaluate the effect of RA on cell migration, HNSCC cells were treated with 80 μg/ml RA from 24 h to 72 h. RA significantly reduced migration of UM-SCC-6 cells up to 48 hrs and reduced UM-SCC-10B cell migration as late 72 hours as shown in Figures 3A and 3B, respectively.…”

Section: Ra Reduces Cell Migrationmentioning

confidence: 99%

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Tumur¹,

Guerra²,

Yanni³

et al. 2015

J Cancer Sci Ther

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Objective: Active components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. Rosmarinic acid (RA), a phenolic compound in various herbal plants, is well-recognized for its anti-oxidant, anti-inflammatory, anti-proliferative properties in a variety of cell types. In this report, we describe a novel role for RA as an inhibitor of epidermal growth factor (EGF) stimulated signaling in HNSCC and propose a cellular reactive oxygen species (ROS)-mediated mechanism for the observed effects.Methods: Cellular growth, migration and reactive oxygen species (ROS) profiles were examined in RA-treated and untreated HNSCC cell lines (UM-SCC-6 and UM-SCC-10B) using the WST-1 viability assay, established in vitro migration assays, and the CM-H2DCFDA ROS assay, respectively. The influence of RA on EGF-stimulated phosphorylation and its downstream pathways was evaluated using Western-blotting techniques.Results: RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines. Furthermore, RA inhibited EGF-induced phosphorylation of the EGFR at tyrosine residues 992 and 845, which led to downregulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ ERK) pathways.Conclusions: This is the first report describing both growth-and motility-inhibitory roles for RA in HNSCC cells. Additionally, our study is the first to demonstrate that treatment with RA can reduce EGF-induced activation of PI3K/ Akt in tumor cells. The present data suggests that RA holds promise as a chemotherapeutic agent against HNSCC. a novel strategy to down-regulate EGFR signaling using the phenolic compound, rosmarinic acid. RosmarinicActive components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. One such food component, rosmarinic acid (RA), is a widely distributed phenolic compound in various herbal plants such as rosemary, sweet basil, sage, mint, and perilla (Figure 1) [10,11]. RA is regarded as a daily-consumed safe ingredient, due to its extensive use in the food industry for flavoring, but studies have also elucidated a medicinal role for RA, especially in regard to its anti-oxidant, and anti-inflammatory activities [12,13]. Furthermore, an emerging body of literature has also described the growth inhibitory and anti-invasion properties of RA in colon, skin, breast and ovarian cancers in vitro and/or in vivo [14][15][16][17][18][19], but the mechanisms underlying these effects are poorly understood. A chemopreventive role for RA in HNSCC has been described in 7,12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis [20], but a chemotherapeutic role for RA in the treatment of HNSCC has not yet been reported.Given the anti-oxidant properties attributed to RA, it is possible that RA's anti-tumor effects stem from its ability to combat oxidative stress in HNSCC. Oxidative ...

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Section: Angiogenic Factorsmentioning

confidence: 99%

“…Overexpression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), promoters of angiogenesis, occur in SCC [11]. EGFRvIII leads to autoactivation and upregulated VEGF and tissue factor (TF) further augmenting this pathway [11]. Hypoxia is also a strong driving force in tumor angiogenesis and the associated transcription factor, hypoxia inducible factor-1 (HIF-1) is over-expressed and at the top of a cascade of inducible proangiogenic proteins contributing to angiogenesis in HNSCC.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Integration of Biomarkers Including Molecular Targeted Therapies in Head and Neck Cancer

Williams

2010

Head and Neck Pathol

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Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway, angiogenesis, and epithelial to mesenchymal transition. Over-expression and mutations of genes in these pathways including EGFR, VEGF, HER2, BRAF and RET, contribute to tumorigenesis in head and neck cancers from squamous carcinomas, to salivary adenocarcinomas and thyroid carcinomas, both follicular and c-cell derived. Monoclonal antibodies to the EGFR receptor and oral tyrosine kinase inhibitors are currently being studied in multiple phase II and III clinical trials to determine their efficacy in head and neck cancers and correlative studies for biomarkers are on-going.

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Molecular mediators of metastasis in head and neck squamous cell carcinoma

Abstract: Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination.

Cited by 67 publications

References 56 publications

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Integration of Biomarkers Including Molecular Targeted Therapies in Head and Neck Cancer

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