Metastasis-Related Differences in Gene Expression Profiles of Oral Cancer Cell Lines

Changes in expression levels of specific genes within a primary tumor lead to heterogeneity within the tumor cells, generating cell populations capable of metastasis. Objective: Using the Affymetrix HuFL oligonucleotide microarrays which contain probes for 6800 known human genes, we compared the gene expression profiles of two pairs of primary (MDA-686Tu and MDA-1386Tu) and metastatic (MDA-686Ln and MDA-1386Ln) oral cancer cell lines. Each pair of primary and metastatic cell lines was derived from the same patient. Method: Gene expression patterns were compared by two methods. 1: We selected the top 50% highly-expressed genes (686Tu=205; 1386Tu=52; 686Ln=234; 1386Ln=86) for each cell line based on hybridization signal intensity, and compared expression between the pairs of oral cancer cell lines. Results: From this data, we identified 37 and 71 highly-expressed genes specific for primary and metastatic cell lines, respectively. 2. Fold-change analysis between primary and metastatic cell lines revealed 264 (3.9%) (181 genes down- and 83 genes up-regulated) and 587 ( 8.6%) (230 down- and 357 genes up-regulated) genes that are differentially expressed by two-fold or greater for the MDA-686 pair and the MDA-1386 pair, respectively. A number of these differentially-expressed genes have previously been linked with tumor metastasis. Differential expression of selected genes was confirmed by RT-PCR and Western and immunostaining analyses of these cell lines and of archival tumor specimens from which these cell lines were derived. Among these differentially- expressed genes, only 19 (0.3%) (8 down -and 11-up-regulated) were common for both pairs of cell lines. Conclusion: Our data suggest that metastasis-related differential gene expression in oral cancer is highly heterogenous and varies significantly between patients.