Down-regulation of Immune-related Genes by PSCA in Gallbladder Cancer Cells Implanted into Mice

Anticancer Res. 2015 May;35(5):2619-25.

Abstract

Background/aim: In previous work, we found that prostate stem cell antigen (PSCA) gene, encoding a glycosylphosphatidylinositol-anchored protein, is a presumable tumor suppressor in gastric cancer and gallbladder cancer (GBC). The introduction of PSCA cDNA into GBC cell lines significantly suppressed tumorigenecity of cells in mice. The PSCA protein is thought to be involved in some form of intracellular signaling that remains to be elucidated.

Materials and methods: Using microarrays, we conducted gene-expression profiling on tumors generated by a GBC cell line TGBC-1TKB, with and without expression of PSCA, which was implanted into mice. Genes whose expression was down-regulated by PSCA were selected, and their down-regulation was confirmed by real-time PCR.

Results: We identified several immune-related genes down-regulated by PSCA, including interleukin 8 (IL8), IL1 receptor antagonist (IL1RN) and S100 calcium-binding proteins A8 (S100A8) and A9 (S100A9).

Conclusion: PSCA signaling may suppress tumor growth in vivo by modulating immunological characteristics of GBC cells.

Keywords: GPI-anchored protein; Prostate stem cell antigen; gallbladder cancer; intracellular signaling; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Calgranulin A / biosynthesis
  • Calgranulin A / immunology
  • Calgranulin B / biosynthesis
  • Calgranulin B / immunology
  • Cell Line, Tumor
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / immunology
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Glycosylphosphatidylinositols / biosynthesis*
  • Glycosylphosphatidylinositols / genetics
  • Glycosylphosphatidylinositols / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / biosynthesis
  • Interleukin 1 Receptor Antagonist Protein / immunology
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Mice
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology

Substances

  • Antigens, Neoplasm
  • Calgranulin A
  • Calgranulin B
  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-8
  • Neoplasm Proteins
  • PSCA protein, human