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Primary cilia are increased in number and demonstrate structural abnormalities in human cancer
  1. Binnaz Yasar1,
  2. Kim Linton2,3,
  3. Christian Slater1,
  4. Richard Byers3,4,5
  1. 1Division of Medical Education, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, UK
  2. 2Department of Medical Oncology, The Christie Foundation NHS Trust, Manchester, UK
  3. 3Division of Molecular and Clinical Cancer Studies, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, UK
  4. 4Department of Histopathology, Manchester Royal Infirmary, Manchester, UK
  5. 5Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  1. Correspondence to Dr Richard Byers, Department of Histopathology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK; richard.byers{at}cmft.nhs.uk

Abstract

Aims Primary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples.

Methods Primary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed.

Results Compared with normal tissues, primary cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75% vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively, p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant difference compared with normal control tissue for gastric and prostatic adenocarcinomas or for lobular and ductal breast cancers. Additionally, structural abnormalities of primary cilia were identified in cancer tissues, including elongation of the axoneme, multiple basal bodies and branching of the axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically significant correlation with primary cilia frequency across all tissues (p=0.1501).

Conclusions The results show upregulation of primary cilia and the presence of structural defects in a wide range of human cancer tissue samples demonstrating association of dysregulation of primary cilia with human cancer.

  • CANCER
  • CELL BIOLOGY
  • IMMUNOFLUORESCENCE

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Footnotes

  • Handling editor Runjan Chetty

  • Contributors All authors contributed to the experimental design, data analysis and manuscript writing. BY collected data.

  • Funding This work was supported by Manchester Royal Infirmary Endowment Funds.

  • Competing interests None declared.

  • Ethics approval North West—Haydock Research Ethics Committee reference 03/8/016.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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