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Primary Cilia Are Frequently Present in Small Cell Lung Carcinomas but Not in Non-Small Cell Lung Carcinomas or Lung Carcinoids. 2023

Kazuya Shinmura, and Hisami Kato, and Hideya Kawasaki, and Takahiko Hariyama, and Kimio Yoshimura, and Kazuo Tsuchiya, and Hirofumi Watanabe, and Isao Ohta, and Eri Asahina, and Fumiya Sumiyoshi, and Keisuke Hamada, and Yuichi Kawanishi, and Akikazu Kawase, and Kazuhito Funai, and Haruhiko Sugimura
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: kzshinmu@hama-med.ac.jp.

Most human malignant neoplasms show loss of primary cilia (PC). However, PC are known to be retained and involved in tumorigenesis in some types of neoplasms. The PC status in lung carcinomas remains largely uninvestigated. In this study, we comprehensively assessed the PC status in lung carcinomas. A total of 492 lung carcinomas, consisting of adenocarcinomas (ACs) (n = 319), squamous cell carcinomas (SCCs) (n = 152), and small cell lung carcinomas (SCLCs) (n = 21), were examined by immunohistochemical analysis using an antibody against ARL13B, a marker of PC. The PC-positive rate was markedly higher in SCLCs (81.0%) than in ACs (1.6%) and SCCs (7.9%). We subsequently performed analyses to characterize the PC-positive lung carcinomas further. PC-positive lung carcinomas were more numerous and had longer PC than normal cells. The presence of PC in these cells was not associated with the phase of the cell cycle. We also found that the PC were retained even in metastases from PC-positive lung carcinomas. Furthermore, the hedgehog signaling pathway was activated in PC-positive lung carcinomas. Because ARL13B immunohistochemistry of lung carcinoids (n = 10) also showed a statistically significantly lower rate (10.0%) of PC positivity than SCLCs, we searched for a gene(s) that might be upregulated in PC-positive SCLCs compared with lung carcinoids, but not in PC-negative carcinomas. This search, and further cell culture experiments, identified HYLS1 as a gene possessing the ability to regulate ciliogenesis in PC-positive lung carcinomas. In conclusion, our findings indicate that PC are frequently present in SCLCs but not in non-SCLCs (ACs and SCCs) or lung carcinoids, and their PC exhibit various specific pathobiological characteristics. This suggests an important link between lung carcinogenesis and PC.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002276 Carcinoid Tumor A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182) Argentaffinoma,Carcinoid,Carcinoid, Goblet Cell,Argentaffinomas,Carcinoid Tumors,Carcinoids,Carcinoids, Goblet Cell,Goblet Cell Carcinoid,Goblet Cell Carcinoids,Tumor, Carcinoid,Tumors, Carcinoid
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D002923 Cilia Populations of thin, motile processes found covering the surface of ciliates (CILIOPHORA) or the free surface of the cells making up ciliated EPITHELIUM. Each cilium arises from a basic granule in the superficial layer of CYTOPLASM. The movement of cilia propels ciliates through the liquid in which they live. The movement of cilia on a ciliated epithelium serves to propel a surface layer of mucus or fluid. (King & Stansfield, A Dictionary of Genetics, 4th ed) Motile Cilia,Motile Cilium,Nodal Cilia,Nodal Cilium,Primary Cilia,Primary Cilium,Cilium,Cilia, Motile,Cilia, Nodal,Cilia, Primary,Cilium, Motile,Cilium, Nodal,Cilium, Primary
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D053823 Hedgehog Proteins A family of intercellular signaling proteins that play an important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action. Hedgehog Protein,Hedgehog Protein, Vertebrate,Banded Hedgehog Protein,Desert Hedgehog Protein,Indian Hedgehog Protein,Sonic Hedgehog Protein,Vertebrate Hedgehog Protein,Hedgehog Protein, Banded,Hedgehog Protein, Desert,Hedgehog Protein, Indian,Hedgehog Protein, Sonic,Protein, Hedgehog

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