ESTABLISHMENT, CHARACTERIZATION AND DRUG-SENSITIVITY OF 4 NEW HUMAN SOFT-TISSUE SARCOMA CELL-LINES

Four new cell lines were established from patients with soft tissue sa rcomas. Drug sensitivity as well as genotypic characterization, which may be related to drug sensitivity in these cell lines, was determined . Karyotype, H-ras, c-myc and mutant p53 gene expression, Rb, G(1)- an d S-phase cyclins, E2F and major cyclin/CDK inhibitors such as p16 and p21 and p-glycoprotein were analyzed using cytogenetic, Northern blot and immunological methods. Drug sensitivity was determined using grow th inhibition tests. These cell lines differed in their morphology and growth rates, forming colonies in soft agar with a cloning efficiency of 4.3-13.4%, and 3 of the 4 cell lines grew in nude mice. Cytogeneti c analysis of cell lines revealed highly aneuploid karyotypes. Deletio n and/or translocation of chromosome 17 was seen in HS-16, HS-18 and H S-30 cells, and both copies of chromosome 13 were lost or re-arranged in the HS-18 cell line. Mutant p53 protein was present in all 4 cell l ines. HS-18 cells showed no expression of the Rb protein and high leve rs of expression of E2F, cyclin A, cyclin E and CDK2. HS-16 expressed a higher level of cyclin D than the other 3 cell lines. p21(wafl) expr ession was seen in all cell lines, but p16(ink4) was expressed only in HS-30 and HS-42 cell lines. These cell lines were sensitive to taxol and relatively resistant to methotrexate, vinblastine and 5-fluorourac il when compared with the fibrosarcoma cell line HT-1080. These new ce ll lines should provide a useful model for the study of soft tissue sa rcomas and for evaluating new drugs or treatments. (C) 1996 Wiley-Liss , Inc.