Correlation of the inability to sustain growth in defined serum-free medium with the suppression of tumorigenicity in Wilms' nephroblastoma
✍ Scribed by Steven F. Dowdy; Bernard E. Weissman; Eric J. Stanbridge
- Book ID
- 102885861
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 1006 KB
- Volume
- 147
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
We report the investigation of the growth properties of tumorigenic and reverted nontumorigenic Wilms' nephroblastoma cells when cultured in seruni-free medium. Wilms' tumor, a pediatric nephroblastoma, has been associated with deletionsencompassing the p13 band of chromosome 11 and an independent loss of heterozygosity at 11 p l 5 . Weissman et al. (Science 236:175-180, 1987) transferred a human der(l1) chromosome into the G401.6TG.6 Wilms' tumor cell line via the microcell-mediated chromosome transfer technique. The resulting microcell hybrids were nontumorigenic when assayed in nude mice; however these cells retained all of the in vitro growth and morphological characteristics of the tumorigenic parental cells in 10% fetal calf serum (FCS). Segregation of the der(l1) chromosome from the nontumorigenic microcell hybrid cells resulted in the reappearance of the tumorigenic phenotype in vivo. In vitro culture of these cell lines in serum-free medium supplemented with 0.1 % bovine serum albumin (%A) and 10 ngiml Na, O, Se resulted in sustained growth of both the tumorigenic parent and the tumorigenic segregant while the nontumorigenic microcell hybrids were unable to divide. The separate addition of either 10 ngiml of epidermal growth factor (ELF) or 5 Fgiml of insulin did not alter this effect. However, the addition of 5 pginil of transferrin stimulated the nontumorigenic microcell hybrid cells to grow at a rate comparable to the tumorigenic cells. In addition, conditioned serum-free medium from the tumorigenic parental or tumorigenic segregant cell lines was able to stimulate the growth of the nontumorigenic microcell hybrid cells, whereas the reciprocal experiment had no effect on the growth of the tumorigenic cells. These data suggest that the inability of the microcell hybrid cells to grow in serum-free conditions is correlated with their genetic nontumorigenic phenotype and that a specific growth factor, transferrin, can bypass or alter this negative growth regulatory pathway(s) in vitro.