Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma

Michael E. Kupferman, Vyomesh Patel, Virote Sriuranpong, Panamwat Amornphimoltham, Samar A. Jasser, Mahitosh Mandal, Ge Zhou, Jing Wang, Kevin Coombes, Asha Multani, Sen Pathak, J. Silvio Gutkind, Jeffrey N. Myers

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Oral cavity squamous cell carcinoma (OSCC) is one of the leading causes of cancer deaths worldwide and most of these deaths result from local-regional recurrence and metastases. Evasion of apoptosis is an important hallmark of cancer development and progression, and previous studies have shown that evasion of anoikis, or detachment-induced apoptosis, correlates with a more aggressive phenotype of carcinoma cells in OSCC. To elucidate the cytogenetic and molecular characteristics of anoikis resistance, we generated several cell lines and clones that displayed this cellular phenotype. To test the hypothesis that chromosomal alterations may underlie this phenotypic transformation, we used karyotype analysis to observe changes in the chromosomal structure of anoikis-sensitive and anoikis-resistant cell lines. We further hypothesized that a unique pattern of gene expression was induced by cell-detachment of anoikis-resistant cell lines, and cDNA microarray analysis was performed using a panel of anoikis-resistant oral cancer cell lines grown under attached and detached growth conditions. We identified S100P, KLK6 and CTNNAL1 as genes whose expression levels were differentially regulated in the anoikis-resistant cell lines compared to the anoikis-sensitive cells under detached conditions. These results were verified using real-time RT-PCR. The anoikis-resistant phenotype of squamous cell carcinoma has a distinct genetic expression pattern that is marked by chromosomal alterations that may contribute to differential expression of genes involved in diverse cellular functions. Therapies targeting these potential mediators of anoikis resistance may prove to be beneficial in the treatment of metastatic squamous cell carcinoma.

Original languageEnglish (US)
Pages (from-to)440-454
Number of pages15
JournalOral Oncology
Volume43
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Anoikis
  • Cytogenetics
  • Oral cancer
  • Tongue
  • Tumor progression

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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