Aberrant expression of receptors for platelet-derived growth factor in an anaplastic thyroid carcinoma cell line

Abstract

Receptors for platelet-derived growth factor (PDGF) have previously only been found on cells of mesenchymal and glial origin. This study shows PDGF receptors on an anaplastic thyroid carcinoma cell line, C 643, that was found to express thyroglobulin mRNA, confirming its origin from thyroid epithelium. Northern blot analysis of poly(A)+ RNA hybridized with a human PDGF B-type receptor cDNA probe revealed a 5.4-kilobase transcript in the C 643 cells. The existence of receptor protein on the cell surface was shown by immunofluorescence microscopy with a PDGF receptor monoclonal antibody. Binding experiments with 125I-labeled dimeric forms of PDGF indicated that the cells contain B-, but not A-, type PDGF receptors. The addition of PDGF to C 643 membranes in the presence of [32P]ATP induced phosphorylation of the receptor. A polyclonal PDGF B-type receptor peptide antiserum was used to immunoprecipitate a receptor protein from metabolically labeled C 643 cells; the receptor was found to be 5-10 kDa larger than that in normal human fibroblasts. Removal of N-linked carbohydrates using endoglycosidase H resulted in deglycosylated receptor proteins of similar size in C 643 cells and fibroblasts, indicating differences in glycosylation patterns of the two receptor proteins. The aberrant expression of receptors might be crucial in tumor development by conferring a selective growth advantage to the cancer cells.