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Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma.

Authors
  • Yoshimoto, Taichiro1
  • Matsubara, Daisuke1
  • Soda, Manabu2
  • Ueno, Toshihide2, 3
  • Amano, Yusuke1
  • Kihara, Atsushi1
  • Sakatani, Takashi4
  • Nakano, Tomoyuki5
  • Shibano, Tomoki5
  • Endo, Shunsuke5
  • Hagiwara, Koichi6
  • Fukayama, Masashi7
  • Denda-Nagai, Kaori8
  • Irimura, Tatsuro8
  • Mano, Hiroyuki2, 3
  • Niki, Toshiro1
  • 1 Department of Integrative Pathology, Jichi Medical University, Japan. , (Japan)
  • 2 Department of Cellular Signaling, The University of Tokyo, Japan. , (Japan)
  • 3 Division of Cellular Signaling, National Cancer Center Research Institute, Japan. , (Japan)
  • 4 Department of Diagnostic Pathology, Nippon Medical School Hospital, Japan. , (Japan)
  • 5 Department of Thoracic Surgery, Jichi Medical University, Japan. , (Japan)
  • 6 Division of Pulmonary Medicine, Department of Internal Medicine, Jichi Medical University, Japan. , (Japan)
  • 7 Human Pathology, Graduate School of Medicine, The University of Tokyo, Japan. , (Japan)
  • 8 Division of Glycobiologics, Intractable Disease Research Center, Juntendo University, Japan. , (Japan)
Type
Published Article
Journal
Cancer science
Publication Date
Sep 01, 2019
Volume
110
Issue
9
Pages
3006–3011
Identifiers
DOI: 10.1111/cas.14129
PMID: 31301084
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell-cell and cell-matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O-glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness. © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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