title: Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma.
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.
authors.affiliation: Department of Head and Neck Surgery, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Unit 441, Houston, TX 77030, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kupferman
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.forename: Panamwat
authors.initials: P
authors.lastname: Amornphimoltham
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
authors.forename: Ge
authors.initials: G
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Coombes
authors.forename: Asha
authors.initials: A
authors.lastname: Multani
authors.forename: Sen
authors.initials: S
authors.lastname: Pathak
authors.forename: J
authors.initials: J
authors.lastname: Silvio Gutkind
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction