Transcriptome of Oral Cancer Cells Adapted to Suspension Culture Is Potentially Related to Cancer Progressive Phenotypes.

Abstract

Cervical lymph node metastasis worsens oral cancer prognosis. Cancer cells with high metastatic ability can delay or resist apoptosis and survive in the floating condition during circulation. The involved genes and pathways in this process remain largely unknown. This study aimed to establish an oral cancer cell line adapted to suspension culture by in vitro selection and perform gene expression analysis. The oral cancer cell subline adapted to suspension culture was isolated by in vitro selection from the oral cancer cell line, HSC-3. The transcriptome profiles of HSC-3 and its subline were compared using gene expression microarrays. Gene Ontology (GO) enrichment analysis, Gene Set Enrichment Analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were performed to predict the involved pathways and molecules in cancer progression. The subline was designated as HSC-3S5 The cellular viability of HSC-3S5 cells at the suspension culture was higher than that of HSC-3 cells. A total of 961 genes were differentially expressed between HSC-3 and HSC-3S5 cells under the threshold cut-off (FDR-adjusted p-value of <0.05 and absolute fold change of >1.5). GO terms, such as growth regulation, were enriched in the DEGs. GSEA revealed the association between the DEGs and significant gene sets, including metastasis and stemness. IPA predicted that the proliferation-related pathways were enhanced while the apoptotic pathway was inhibited in HSC-3S5 cells compared to HSC-3 cells. Our transcriptome analysis revealed several potentially activated pathways and molecules in the floating-adapted oral cancer cells and indicated molecular implications for cancer progression.