title: Neuroendocrine-specific protein (NSP)-reticulons as independent markers for non-small cell lung cancer with neuroendocrine differentiation. An in vitro histochemical study.
abstract: Neuroendocrine-specific protein (NSP)-reticulons have recently been discovered and were shown to exhibit a restricted, neuroendocrine/neural-specific expression pattern. These protein aggregates are anchored to the membranes of the endoplasmic reticulum and occur in small cell lung cancer (SCLC), but not in typical non-SCLC. In the current study we have examined the occurrence of NSP-reticulons in non-SCLC cell lines known to express neuroendocrine features (non-SCLC-NE). NSP-reticulon expression was observed in all three non-SCLC-NE cell lines studied, albeit with variable intensity and in varying numbers of cells. Western blot analysis confirmed the presence of NSP-reticulon expression in these non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A type. When compared to conventional neuroendocrine markers, NSP-reticulons revealed a distinct staining profile, showing only partial overlap with the other markers. The non-SCLC-NE cell lines combined these neuroendocrine characteristics with some features of non-SCLC. We conclude that NSP-reticulon expression is restricted to lung carcinoma cells with a neuroendocrine phenotype and predict that these constituents may become clinically relevant markers for the detection of neuroendocrine differentiation in solid tumours.
authors.affiliation: Department of Molecular Cell Biology and Genetics, Universiteit Maastricht, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Senden
authors.forename: I
authors.initials: I
authors.lastname: Linnoila
authors.forename: E
authors.initials: E
authors.lastname: Timmer
authors.forename: H
authors.initials: H
authors.lastname: van de Velde
authors.forename: A
authors.initials: A
authors.lastname: Roebroek
authors.forename: W
authors.initials: W
authors.lastname: Van de Ven
authors.forename: J
authors.initials: J
authors.lastname: Broers
authors.forename: F
authors.initials: F
authors.lastname: Ramaekers
mesh_terms: D014408:Biomarkers, Tumor; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000737:chemistry; D006651:Histocytochemistry; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C081781:RTN1 protein, human