Endothelin-secreting tumors and the idea of the pseudoectopic hormone secretion in tumors

Ectopic hormone secretion in tumor cells is here described as an amplificat ion of hormone production already present in normal, nonendocrine tumor-ori ginated tissue. This idea is tested on the available data regarding endothe lin-l (ET-I) secreting tumors. The endothelins are ubiquitous regulatory pe ptides produced by various tissues. The precursor cells of many tumor types secrete endothelins. ET-1 protein expression was detected in situ in all t ested prostate cancers as well as in normal prostate tissue. The majority o f hepatocellular carcinomas produce ET-I, while ET-1 is secreted by the nor mal hepatic stellate cells. Human breast cancer cells produce immunoreactiv e ET-I. Similar data exist for pancreatic tissue, the thyroid and large bow el. We can conclude that tumor cells might sustain endothelin secretions al ready present in the normal tumor-originated tissue. The model that is pres ented of the pseudoectopic hormone secretion consists of relations between a few parameters. The proportion of hormone-secreting tumors (T-h) among al l tumors (T) of that organ depends on the amount of the hormone-secreting c ells (C-h) among all cells (C) susceptible to malignant transformation. The corrective factor (k) was introduced in the expression T-h/T=C-h/C*k to re present specific conditions altering the malignant transformation probabili ty for a certain normal hormone-secreting cell. In prostate, breast and col on, the k value is predicted to be similar to 1, suggesting that ET-l-secre ting normal cells are not more prone to the malignant transformation than t heir neighbours. In liver and pancreas, the incidence of ET-l-secreting tum ors outnumbers the proportions of normal ET-l-secreting cells (k values sim ilar to 1). In these organs, normal ET-l-secreting cells seem more likely t o turn malignant in comparison to their neighbours, perhaps due to their fu nction, position and exposition to oncogenic factors, or even due to their ET-1 secretion. There are similar data for thyroid and adrenal glands. No E T-I secretion was reported in kidney neoplasms. Normal renal ET-1 secreting cells might be less prone to turn malignant than other renal cells. Unlse the normal lung tissue, small cell lung cancers often secrete adrenocortico trophic hormone (ACTH). The pancreatic islet cells do not secrete gastrin, but their tumors often do. Constant k would exceed 1 in both cases. We spec ulate that these tumors might originate from a small subset of cells with t he described feature. Tumor cells sometimes lack features of the normal tis sue, as in the cases of the steroid receptor-negative breast cancer. These tumors might originate from the hypothetical subset of receptor-free breast cells, Benign breast epithelial cells lacking oestrogen receptors have bee n described in cases of megalomastia. These cells might be constituents of normal breasts or, perhaps, present only in cases of increased breast cance r risk.