Mucin 1 and poly I:C activates dendritic cells and effectively eradicates pituitary tumors as a prophylactic vaccine

Mol Med Rep. 2016 Apr;13(4):3675-83. doi: 10.3892/mmr.2016.4964. Epub 2016 Mar 2.

Abstract

Pituitary tumors are the most common type of cancer within the central nervous system. In the present study, the expression levels of mucin 1 (Muc1) were examined in invasive and non‑invasive pituitary tumor samples, and the results of immunohistochemical staining and Western blot analysis demonstrated marked positive expression of Muc1. In addition, Muc1 + polyinosinic:polycytidylic acid (poly I:C) was found to stimulate the expression levels of the surface molecules cluster of differentiation (CD)40, CD83 and CD80, and HLA‑DRm and decreased the expression of CD14 in the dendritic cells, determined using fluorescence‑activated cell sorting. The secretions of interleukin (IL)‑6, tumor necrosis factor‑α and IL‑1β cytokines were also significantly induced, in a dose‑dependent manner. In in vivo experiments, a higher percentage of CD3+CD4+ T lymphocytes was detected, and the levels of interferon‑γ and IL‑2 in the splenocytes were also upregulated. Furthermore, the combination treatment of Muc1 with poly I:C increased anti‑Muc1 IgM and anti‑Muc1 IgG titers, and altered the balance of IgG2a and IgG1, all of which increased the T helper (Th)1 polarized immune response. Thus, the tumor antigen, Muc1, with poly I:C may produce potent protective effects, which polarize immune responses towards Th1, and elicit antitumor immunity to inhibit the progression of pituitary tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / blood
  • Antigens, CD / metabolism
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Interferon-gamma / analysis
  • Interleukin-2 / analysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Mucin-1 / pharmacology*
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology
  • Pituitary Neoplasms / prevention & control*
  • Poly I-C / pharmacology*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects

Substances

  • Antibodies
  • Antigens, CD
  • Cancer Vaccines
  • Interleukin-2
  • Mucin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Poly I-C