Identification of genes associated with enhanced metastasis of a large cell lung carcinoma cell line.

We have compared the transcriptional profile of large cell lung tumor cell lines NIH-H460 and H460-M making use of the Affymetrix GeneChip system. H460-M is derived from NIH-H460 and displays enhanced experimental and spontaneous metastasis in nude mice. Out of the 12,600 genes investigated, 73 (0.6%) were up-regulated and 114 (0.9%) were down-regulated on the basis of the scoring criteria. We have classified the de-regulated genes according to the following categories: immune response, enzymes, modulation of transcription, signal transduction, cytoskeleton/adhesion and extracellular matrix associated proteins, cell-cycle/apoptosis, transporters and 'others'. Among the remarkable features of this system are the up-regulation of the steady-state mRNA levels of neuroendocrine markers such as neurotensin (NTS), neuroendocrine-specific protein (NSP), neural cell adhesion molecule 1 (NCAM1) and gamma-aminobutyric acid B-type receptor (GPR51) in cell line H460-M. Semaphorin 3B (SEMA3B) was dramatically down-regulated in cell line H460-M and emerged as the most interesting gene for target validation.