Silencing Met receptor tyrosine kinase signaling decreased oral tumor growth and increased survival of nude mice

X. Tao, K. S. Hill, I. Gaziova, S. K. Sastry, S. Qui, P. Szaniszlo, S. Fennewald, Vicente Resto, Lisa Elferink

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objectives: The hepatocyte growth factor receptor (Met) is frequently overexpressed in Head and Neck Squamous Cell Carcinoma (HNSCC), correlating positively with high-grade tumors and shortened patient survival. As such, Met may represent an important therapeutic target. The purpose of this study was to explore the role of Met signaling for HNSCC growth and locoregional dissemination. Materials and methods: Using a lentiviral system for RNA interference, we knocked down Met in established HNSCC cell lines that express high levels of the endogenous receptor. The effect of Met silencing on in vitro proliferation, cell survival and migration was examined using western analysis, immunohistochemistry and live cell imaging. In vivo tumor growth, dissemination and mouse survival was assessed using an orthotopic tongue mouse model for HNSCC. Results: We show that Met knockdown (1) impaired activation of downstream MAPK signaling; (2) reduced cell viability and anchorage independent growth; (3) abrogated HGF-induced cell motility on laminin; (4) reduced in vivo tumor growth by increased cell apoptosis; (5) caused reduced incidence of tumor dissemination to regional lymph nodes and (6) increased the survival of nude mice with orthotopic xenografts. Conclusion: Met signaling is important for HNSCC growth and locoregional dissemination in vivo and that targeting Met may be an important strategy for therapy.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalOral Oncology
Volume50
Issue number2
DOIs
StatePublished - Feb 2014

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Keywords

  • Head and neck squamous cell carcinoma
  • HGF receptor
  • MET
  • Oral cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

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