Effects of sodium butyrate on synthesis of human chorionic gonadotrophin in trophoblastic and non-trophoblastic tumours

Abstract

SOME human tumours and tumour-derived cell lines are capable of producing ‘eutopic’ peptide hormones and other proteins that are normally synthesised by the tissue from which the tumour originated. For example, choriocarcinoma cells, which are derived from cancer of the placental trophoblast, can synthesise human chorionic gonadotrophin (hCG) (refs 1, 2), and cultured pituitary adenomas can produce growth hormone (GH) (ref. 3). On the other hand, it is well established that a variety of malignant human tumours can produce ‘ectopic’ peptide hormones and other proteins which are not normally associated with the tissue of origin^4–8. Ectopic synthesis of placental proteins, including the placental isoenzyme of alkaline phosphatase as well as the hormones hCG and human placental lactogen, may provide specific markers for neoplasm, since these proteins are not normally found in measurable amounts in the serum of men or of non-pregnant women⁹. Several human glycoprotein trophic hormones, including hCG, thyroid-stimulating hormone (TSH), luteinising hormone (LH), and follicle-stimulating hormone (FSH), are composed of two non-identical subunits, α and β (refs 10–13). These four hormones have virtually identical α subunits; in contrast each has a unique β subunit, which is responsible for biological specificity¹². Complete hCG and free subunits are secreted by normal and neoplastic placenta^1,2,14 and by many non-trophoblastic tumours^15,16. Since hCG is a eutopic hormone for trophoblastic tumours, but an ectopic hormone for non-trophoblastic tumours, it occured to us that its synthesis by the two types of tumours might be regulated differently. We therefore compared the synthesis of hCG and hCG-α by three choriocarcinoma cell lines—BeWo (ref. 1), JEG-3 (ref. 2) and Reid (P. O. Kohler, unpublished observations)—with the synthesis by two non-trophoblastic tumour-derived cell lines—ChaGo and HeLa. (ChaGo was derived from an hCG-producing pulmonary carcinoma¹⁶, and HeLa from a carcinoma of the cervix¹⁷.) We also tested the effects of sodium butyrate on the synthesis, since this compound had been shown to induce hCG-α and hCG synthesis in certain HeLa cells¹⁸. We found that in the absence of inducer, all of the cell lines can produce hCG-α—the trophoblastic tumour cells at roughly comparable rate, but the non-trophoblastic tumour cells at widely different rates (Fig. 1).