Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis

Oncotarget. 2015 Dec 8;6(39):42105-17. doi: 10.18632/oncotarget.5870.

Abstract

P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R-silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF-based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP-1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis.

Keywords: P2X7R; TCP-1; lymphatic-metastasis; lymphoma; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Chaperonin Containing TCP-1 / genetics*
  • Chaperonin Containing TCP-1 / metabolism
  • Down-Regulation*
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Lymphoma / genetics*
  • Lymphoma / metabolism
  • Lymphoma / therapy
  • Male
  • Mice, Inbred DBA
  • Middle Aged
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / therapy
  • Proteomics / methods
  • RNA Interference*
  • RNAi Therapeutics
  • Receptors, Purinergic P2X7 / genetics*
  • Receptors, Purinergic P2X7 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Young Adult

Substances

  • Receptors, Purinergic P2X7
  • Chaperonin Containing TCP-1