Peptide Hormone Production Associated with Small Cell Lung Cancer

Abstract

Small cell lung cancer (SCLC) is frequently associated with polypeptide hormone production, and a number of paraneoplastic syndromes have been reported. The neoplasia is thought to originate in the so-called Kulchitsky or K cells, small granular basal cells with endocrine properties found in the tracheobronchial mucosa (Tischler 1978). These K cells and the related SCLC and carcinoid tumor cells share APUD cell characteristics, such as cytoplasmic and membrane-bound dense core (“neurosecretory”) granules, amine precursor uptake and decarboxylation of precursors to biogenic amines by l-dopa decarboxylase, and storage of amines and polypeptide products in the neurosecretory granules (Pearse 1969). It has therefore been suggested that APUD cells and their tumors have a neuroepithelial origin different from the endodermal origin of the rest of the respiratory mucosa and its related neoplasia, such as squamous cell carcinoma and adenocarcinoma (Pearse 1969). However, morphological findings of foci of squamous carcinoma and adenocarcinoma in SCLC (Carney et al. 1982), the simultaneous appearance of histologically different multiple lung cancer (Gazdar et al. 1981), and ultrastructural evidence that SCLC cells may undergo squamous cell metaplasia (Mackay et al. 1977) favor the hypothesis that all bronchial mucosa cells and the tumors arising from them have a common origin. Although polypeptide hormone production is more frequently associated with SCLC, other types of lung cancer with non-APUD cell characteristics frequently show hormone secretion (Rose 1979). Furthermore, hormonal peptides are produced by a number of other solid tumors, by lymphomas, and by different types of leukemia (Pflüger et al. 1981, 1982).