Mechanisms of antitumor and immune-enhancing activities of MUC1/sec, a secreted form of mucin-1

Dan Ilkovitch, Roberto Carrio, Diana M. Lopez

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Mucin 1 (MUC1) is a polymorphic type 1 transmembrane protein found on the apical surface of normal cells lining the lumen of ducts and glands. Mucins are thought to provide mucosal protection from environmental exposures and carcinogens. An altered form of the MUC1 glycoprotein, which is hypoglycosylated, is expressed in several types of human cancers. In our laboratory, we have found that transfection of a murine mammary tumor cell line with a human secreted isoform of MUC1 rendered these DA-3 cells (DA-3/sec) incapable of growing in intact BALB/c mice. In contrast, implantation of DA-3 cells transfected with the human transmembrane isoform of MUC1 (DA-3/TM), resulted in tumor formation and ultimately death of the animals, similar to the DA-3 parental line. Importantly, inoculation of the DA-3/sec cells in immunodeficient nude mice resulted in tumor formation, indicating that the MUC1/sec molecule's antitumor activity is immunologically controlled. In this review, we summarize the studies we have performed to elucidate possible mechanisms for the immune-mediated antitumor effect of MUC1/sec and/or a unique peptide present in this mucin. Understanding these mechanisms may provide new immunotherapeutic approaches that could be used to target different types of cancer.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalImmunologic Research
Volume57
Issue number1-3
DOIs
StatePublished - Dec 1 2013

Keywords

  • Antitumor activity
  • CCL2
  • Immune-enhancing peptide
  • MUC1 secreted form
  • Mucins
  • Myeloid-derived suppressor cells
  • STATs
  • Urokinase plasminogen activator

ASJC Scopus subject areas

  • Immunology

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