Collapsin Response Mediator Protein-1 and the Invasion and Metastasis of Cancer Cells

Background: Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL1–0, CL1–1, CL1–5, and CL1–5-F4 in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize. Methods: We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL1–5 cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription–polymerase chain reaction (RT–PCR). All statistical tests were two-sided. Results: Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL1–5 cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P