endothelin-1 and Carcinoma--Small-Cell

Prostate growth and development are primarily under the control of androgens; however, other factors can also influence prostatic growth through alternative pathways. This article discusses some of the major nonandrogenic mediators of prostate growth. Information on the pathways by which these factors exert their effects is also reviewed.

Topics: Adenocarcinoma; Androgens; Animals; APUD Cells; Bombesin; Carcinoma, Small Cell; Chromosomes, Human; Cytokines; Endothelin-1; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Hormones; Humans; Insulin-Like Growth Factor Binding Proteins; Male; Neoplasms, Hormone-Dependent; Organ Specificity; Prostate; Prostatic Neoplasms; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Receptors, Transforming Growth Factor beta; Somatomedins; Transforming Growth Factor beta; Tumor Cells, Cultured

Lung cancer, particularly small cell lung cancer (SCLC), is characterized by production of numerous peptides and their resulting clinical syndromes. Such peptides can act as autocrine growth factors for these tumors. In this study, we investigated the role of endothelin (ET)-1 in lung cancer. Using reverse transcription/polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunocytochemistry, we screened a panel of lung cancer cell lines for ET-1, its receptors, and endothelin converting enzyme-1 (ECE-1), which generates the active form of ET-1. ET-1 messenger RNA was expressed in five of seven SCLC, four of four non-small cell lung cancer (NSCLC), and human bronchial epithelial (HBE) cells. The intracellular isoform of ECE-1, important in processing ET-1 if an autocrine growth loop is to function, was downregulated in the lung cancer cell lines as compared with expression of the extracellular isoform. Endothelin A receptor (ETAR), which mediates the mitogenic effects of ET-1 in prostate and ovarian cancer, was upregulated in HBE cells compared with expression in three of seven SCLC and two of four NSCLC cell lines. Endothelin B receptor (ETBR) was more widespread, being expressed in seven of seven SCLC, four of four NSCLC, and the HBE cells. We used flow cytometry to measure mobilization of intracellular calcium as a functional assay for the ETAR. These data concurred with the RT-PCR results, indicating that the ETAR was downregulated or was involved in an alternative signal transduction pathway in lung cancer, and no evidence of functional receptor mediating an autocrine growth loop was found. From our study, the data do not support the putative functional autocrine growth role of ET-1 in lung cancer. We propose instead that ET-1 may act as a paracrine growth factor for surrounding epithelial and endothelial cells via alternative pathways, promoting angiogenesis and stromal growth.

Topics: Aspartic Acid Endopeptidases; Autocrine Communication; Bronchi; Calcium Signaling; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Endothelin-1; Endothelin-Converting Enzymes; Enzyme Induction; Enzyme-Linked Immunosorbent Assay; Epithelium; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Lung Neoplasms; Metalloendopeptidases; Microscopy, Fluorescence; Models, Biological; Neoplasm Proteins; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

In order to study endothelin-1 (ET-1) positive expression in lung cancer and the relationship between the ET-1 quantitative analysis and the types, grades of lung cancer.. ET-1 positive expression and quantitative analysis were detected using avidin-biotin-peroxidase complex method and image analysis technology.. The ET-1 positive expression were mainly located in the cytoplasm in 104 cases with various types of lung cancer. The positive rate of ET-1 in adenocarcinoma, squamous-cell carcinoma and large-cell-lung cancer were 71.4%, 57.1% and 40.0% respectively. The positive rate of ET-1 in small-cell-lung cancer was 21.4%, significantly lower than others. The results of image analysis on adenocarcinoma and squamous-cell carcinoma showed that the lower lung cancer differentiation, the higher ET-1 quantitative.. There is ET-1 positive expression in all of types of lung cancer, but there is a high ET-1 positive expression in adenocarcinoma and squamous-cell carcinoma. The results of image analysis indicated that ET-1 quantitive expression was somehow related to the differentiation degree of neoplasm, so ET-1 quantitative analysis may be as a monitoring index of adenocarcinoma and squamous-cell carcinoma growing.

Topics: Adenocarcinoma; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Endothelin-1; Humans; Lung Neoplasms