GROWTH-FACTOR PRODUCTION BY HUMAN THYROID-CARCINOMA CELLS - ABUNDANT EXPRESSION OF A PLATELET-DERIVED GROWTH FACTOR-B-LIKE PROTEIN BY A HUMAN PAPILLARY CARCINOMA CELL-LINE

As papillary thyroid carcinoma cells grow surrounding finger-like stru ctures of stromal tissue, we postulated they may secrete a growth fact or(s) for mesenchymal cells and that these would be distinct from any mitogenic factors elaborated by follicular carcinomas. Conditioned med ium from both the human papillary carcinoma cell line NPA and the foll icular carcinoma cell line WRO evoked a 20- to 30-fold increase in [H- 3]thymidine incorporation into NIH3T3 cell DNA. NPA cell growth factor activity largely eluted with 0.5 mol/L NaCl from a heparin-Sepharose column. NPA-conditioned medium competed in a platelet-derived growth f actor-B (PDGF-B) RRA, and the mitogenic activity was partially blocked by an anti-PDGF-BB antibody. An immunoprecipitated PDGF-B-like protei n from NPA cells was about 17 kilodaltons in a reducing gel, but, in c ontrast to wild-type PDGF-BB, did not change its electrophoretic mobil ity in an unreduced sodium dodecyl sulfate-polyacrylamide gel electrop horesis. NPA cells expressed an abundant 1.4-kilobase RNA that hybridi zed to probes for the 5'-untranslated and amino-terminal domains of PD GF-B and was distinct from the 4.2-kilobase wild-type PDGF-B chain tra nscript. There were no structural changes in the PDGF-B gene, as deter mined by cytogenetic analysis and restriction mapping. However, the PD GF-B gene in the NPA cells was hypomethylated compared to that in norm al thyroid tissue or WRO cells. In contrast, the mitogenic activity of WRO cells bound to heparin with high affinity and was blocked by a ba sic fibroblast growth factor (bFGF) antibody. WRO cells contained abun dant bFGF mRNA. Both cell lines abundantly expressed transforming grow th factor-beta mRNA. Thus, NPA and WRO cells express powerful, yet dis tinct, mesenchymal cell growth factors. Whereas WRO cells express abun dant bFGF, NPA cells produce a novel PDGF-B-like protein, which may co rrespond to a mutated form of PDGF-B-chain.