Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma. Issue 9 (16th August 2019)

• Record Type: Journal Article
• Authors: Yoshimoto, Taichiro; Matsubara, Daisuke; Soda, Manabu; Ueno, Toshihide; Amano, Yusuke; Kihara, Atsushi; Sakatani, Takashi; Nakano, Tomoyuki; Shibano, Tomoki; Endo, Shunsuke; Hagiwara, Koichi; Fukayama, Masashi; Denda‐Nagai, Kaori; Irimura, Tatsuro; Mano, Hiroyuki; Niki, Toshiro
• Is Part Of: Cancer science. Volume 110:Issue 9(2019)
• Page Start: 3006
• Page End: 3011
• Publication Date: 2019-08-16
• Subjects: adenocarcinoma -- cell adhesion -- lung cancer -- MUC21 -- STAS; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14129
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : We describe a rare histological variant of lung adenocarcinoma consisting of individual cancer cells spreading in alveolar spaces in an incohesive pattern that represents an extreme case of "spread through air spaces" (STAS). This histological pattern is not listed in the WHO classification, and only a few cases have been reported in English literature. In the present study, a whole genomic analysis and immunohistochemical validation allowed us to identify mucin 21 (MUC21) as a molecule associated with cell incohesiveness and STAS in lung adenocarcinoma. This is the first report showing the molecular mechanism of cell incohesiveness of lung adenocarcinoma.