{"title":"Subcellular localization of pro-gastrin releasing peptide in human Ewing sarcoma cell lines.","authors":"Koji Muramatsu, Kouji Maruyama, Yosuke Honda, Hirohisa Katagiri, Yu Takahashi, Naoki Takahashi, Katsumi Aoyagi, Kenichi Mori, Mitsuru Takahashi, Toru Kameya, Takashi Sugino, Ken Yamaguchi","doi":"10.1007/s00795-025-00426-2","DOIUrl":null,"url":null,"abstract":"<p><p>Progastrin-releasing peptide (ProGRP), a neuropeptide, is a stable tumor marker for small cell lung carcinoma (SCLC) and other neuroendocrine tumors, such as medullary thyroid carcinoma. It has recently been reported as highly expressed in Ewing sarcoma (ES) and as a useful marker for this type of tumor. However, the mechanisms underlying ProGRP production remain unclear. This study aimed to elucidate its subcellular localization in human ES cell lines. Three ES cell lines (A-673, SK-N-MC, and SK-NEP-1) and one SCLC line (DMS 53) were transplanted into athymic mice. After 3-4 weeks, the tumors were excised, and the expression and localization of ProGRP were examined using immunohistochemistry and immunoelectron microscopy. Immunohistochemistry revealed that all three ES cell lines expressed ProGRP in a dot-like pattern in their cytoplasm, whereas SCLC cells showed a diffuse granular pattern. Immunoelectron microscopy revealed that ProGRP localized in neurosecretory granules (NSGs) in SCLC cells and in autolysosome-like structures in ES cells, with no NSGs observed in the ES cell lines. ES cells secrete high levels of ProGRP, similar to SCLC cells. However, in ES cells, ProGRP is localized in autolysosome-like structures, unlike the NSGs in SCLC, suggesting that ProGRP in ES can be transported and secreted without following the typical pathway for neuropeptides.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2000,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Molecular Morphology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00795-025-00426-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Progastrin-releasing peptide (ProGRP), a neuropeptide, is a stable tumor marker for small cell lung carcinoma (SCLC) and other neuroendocrine tumors, such as medullary thyroid carcinoma. It has recently been reported as highly expressed in Ewing sarcoma (ES) and as a useful marker for this type of tumor. However, the mechanisms underlying ProGRP production remain unclear. This study aimed to elucidate its subcellular localization in human ES cell lines. Three ES cell lines (A-673, SK-N-MC, and SK-NEP-1) and one SCLC line (DMS 53) were transplanted into athymic mice. After 3-4 weeks, the tumors were excised, and the expression and localization of ProGRP were examined using immunohistochemistry and immunoelectron microscopy. Immunohistochemistry revealed that all three ES cell lines expressed ProGRP in a dot-like pattern in their cytoplasm, whereas SCLC cells showed a diffuse granular pattern. Immunoelectron microscopy revealed that ProGRP localized in neurosecretory granules (NSGs) in SCLC cells and in autolysosome-like structures in ES cells, with no NSGs observed in the ES cell lines. ES cells secrete high levels of ProGRP, similar to SCLC cells. However, in ES cells, ProGRP is localized in autolysosome-like structures, unlike the NSGs in SCLC, suggesting that ProGRP in ES can be transported and secreted without following the typical pathway for neuropeptides.
期刊介绍:
Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization.
Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.