Genes that mediate leptomeningeal metastasis from breast and lung solid tumor primaries

Little is understood about the gene expression changes that underlie cancer spread to the cerebrospinal fluid, or leptomeningeal metastasis. Using four cancer cell line models, we empolyed iterative in vivo selection to generate subpopulations of these cell lines able to access the leptomeningeal space and grow once there. We compared the gene expression profile of the terminally selected cells or "Lep" cells with that of the parental or "Par" cells, as well as that of an intermediate stage of in vivo selection or "Int" cells. Analyses for brain parenchymal metastatic derivatives or "BrM" cells were included for comparison. Four different models were employed: Two human breast cancer cell lines, MDA-MB-231 and HCC1954 as well as one human lung cancer cell line, PC9 and a mouse non-small cell lung cancer cell line, Lewis lung carcinoma. Three technical replicates of each Par cell line, two or three biological replicates and two technical replicates of each of the Int and Lep cells were all subjected to analysis.