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Gene expression profiling of HNSCC cells derived from primary and matched metastatic tumors

ABSTRACT: To look at genes/pathways differentially expressed in metastatic and primary tumor cells we performed global gene expression profiling of the 3 sets of HNSCC lines derived from primary tumors and matched metastatic sites. Illumina HT-12 v4 BeadChip arrays were used. The data suggest that HNSCC lines derived from metastatic sites exhibit phenotypes distinct from those found in cells derived from the corresponding primary tumors. Metastatic cell lines upregulated several pathways involved in stem cell self-renewal, invasion and migration, which are well known characteristics of metastatic progression. We conclude that the cell lines derived from primary patient tumors and matched metastatic sites represent a reliable model to study HNSCC metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117753 | GEO | 2018/07/27

REPOSITORIES: GEO

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Project description:Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we identified neurotensin, highly expressed in HNSCCs in comparison with normal tissues, as an invasion-promoting factor in HNSCC by using microarray analysis of clinical samples. Indeed, neurotensin overexpression associated with lymph node metastasis of neck, and tumors exhibiting neurotensin overexpression had a poor distant metastasis-free survival rate. In HNSCC cells which expressed neurotensin receptor 1 (NTSR1), neurotensin promoted cellular invasion, migration, and induction of matrix metalloproteinases transcripts. Disruption of NTSR1 signaling by silencing RNA caused the reversion of the invasion of HNSCC cells. By further microarray analysis using neurotensin-treated cells, neurotensin caused increased expression of genes implicated in tumor progression and metastasis including cell growth, migration, invasion, adhesion, angiogenesis, and apoptosis. Our findings have revealed a critical role of neurotensin/NTSR1 for invasion and migration in the metastatic process of HNSCC. This study raises the possibility that neurotensin/NTSR1 could be used as a possible predictive marker and a molecular therapeutic target in the antimetastatic strategies of HNSCC. Keywords: Identification of a novel therapeutic target for head and neck squamous cell carcinomas A total of 21 primary HNSCC samples were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). 21 samples of normal-appearing mucosa at the margin of the surgical resection several centimeters from the tumor were also collected and designated histologically normal mucosa. 21 HNSCCs and paired normal tissues were used for microarray experiment. The clinicopathological grade was classified according to the criteria of the Japan Society for Head and Neck Cancer. The Ethics Committee of Chiba University approved our study, and informed consent was obtained from all patients for use of their tissue samples and clinical data. Tissue samples were immediately snap frozen in liquid nitrogen and stored at -80Â°C until use.

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Gene expression profiling of HNSCC cells derived from primary and matched metastatic tumors

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