Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4

Cancer Res. 2014 Sep 1;74(17):4796-810. doi: 10.1158/0008-5472.CAN-14-0210. Epub 2014 Jun 24.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however, the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is overexpressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for patients with ccRCC diagnosed with or at risk of developing metastatic disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein / genetics*
  • C-Reactive Protein / metabolism
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism

Substances

  • Nerve Tissue Proteins
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 4
  • neuronal pentraxin
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • C-Reactive Protein