CHARACTERIZATION OF 5 NEW CELL-LINES DERIVED FROM HUMAN PRIMITIVE NEUROECTODERMAL TUMORS OF THE CENTRAL-NERVOUS-SYSTEM

Medulloblastoma (MB) represents the most frequent malignant brain tumo r of childhood but only a few cell lines and animal models of this pri mitive neuroectodermal tumor (PNET) have thus far been established. Us ing specific cell culture conditions, we were able to derive four huma n MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNE T (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undif ferentiated cells that did not express markers of late neuronal or gli al lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neur al cell adhesion molecule, galactocerebroside, G(D2), G(D3), and the A 2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 gre w as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell lin e MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passag ed MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. in to athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological a nd preclinical studies on PNETs.