Primary tumor cells obtained from MNU-induced mammary carcinomas show immune heterogeneity which can be modulated by low-efficiency transfection of CD40L gene

Cancer Biol Ther. 2009 Jan;8(2):136-42. doi: 10.4161/cbt.8.2.7078.

Abstract

The presence of CD40 on carcinoma cells is an important factor for the generation of tumor-specific responses induced by CD40 ligation. In an N-methyl-N-nitrosourea (MNU)-induced autochthonous mammary tumor model, we analyzed the immune features of primary tumor cells. Here, CD40 was frequently detected on the primary tumor cultures and selectively expressed on the malignant mammary tissue in vivo. On the other hand, every mammary tumor cell culture had a heterogeneous and reduced expression of proinflammatory TNFalpha, IL-1beta, IL-6 and CXCL1 cytokines compared to normal mammary epithelial cells. Low-efficiency transfection of CD40 ligand (CD40L) gene enhanced the expression of proinflammatory cytokines in the tumor cells and strengthened allogeneic immune reactions and costimulatory activity which may help overwhelming suppressive features of the tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / toxicity
  • Animals
  • Animals, Outbred Strains
  • CD40 Ligand / genetics*
  • CD40 Ligand / immunology*
  • Carcinoma / chemically induced
  • Carcinoma / genetics
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Culture Media / chemistry
  • Ethidium / metabolism
  • Female
  • Fluorescent Dyes / metabolism
  • Green Fluorescent Proteins / genetics
  • Immunohistochemistry
  • Liposomes
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Methylnitrosourea / toxicity
  • Mucin-1 / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / immunology
  • Transfection / methods

Substances

  • Alkylating Agents
  • Culture Media
  • Fluorescent Dyes
  • Liposomes
  • Mucin-1
  • Recombinant Proteins
  • CD40 Ligand
  • Green Fluorescent Proteins
  • Methylnitrosourea
  • Ethidium