Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Anti-adhesive and anti-apoptotic effect of epiglycanin/mucin 21 (#166)

Jessica Zhao 1 , Yuri Yi 1 , Katrin Ishii-Schrade 1 , Yuan Tian 1 , Kaori Denda-Nagai 1 , Yoshihiro Hayakawa 1 , Tatsuro Irimura 1
  1. The University of Tokyo, Tokyo, Japan

Cell surface expression of epiglycanin, a mucin-like molecule, is implicated with malignant behavior of carcinoma cells, as suggested by its presence on TA3-Ha but not on TA3-St mammary carcinoma cells.  However, the mechanism was not clear due to lack of molecular identification.  We cloned the gene for the core polypeptide of epiglycanin and renamed it as mucin 21 (Muc21).  Muc21 is a membrane-type mucin with tandem repeats of 15 amino acids extremely rich in Ser/Thr.  A cDNA of Muc21 having 84 tandem repeats was constructed and transfected using a Venus vector into HEK 293T cells.  The fluorescent cells, which were considered to express Muc21, were non-adherent.  The transfectants were less adherent to ECM components than mock cells.  Antibody binding to the cell surface integrin subunits was reduced in Muc21 transfectants in a tandem repeat-dependent manner.  We also tested whether Muc21 modulated cell survival by interfering with the cellular apoptotic pathways.  By using Muc21 expressing CHO-K1 cells, we observed the resistance of Muc21 CHO-K1 cells to apoptotic cell death induced by actinomycin D and the functional significance of this anti-apoptotic effect was supported by lower caspase activities compared to control CHO-K1 cells.  The inhibitory effect of Muc21 expression in caspase activation was confirmed in TA3-St mammary carcinoma cells.  These results indicate that Muc21 inhibit actinomycin D-induced caspase activation thereby reducing apoptotic cell death.  Because Muc21 expression is seen on highly malignant cancer cells, the anti-adherent and anti-apoptotic activities of Muc21 might be exploited to therapeutic resistance and/or facilitation of tumor growth and metastasis.

(References:  Codington et al, Carbohydrate Res, 40, 171, 1975; Itoh et al, Glycobiology, 18:74, 2008; Yi et al, J Biol Chem, 285:21233, 2010)