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

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.

• Authors: Christina A von Roemeling, Derek C Radisky, Laura A Marlow, Simon J Cooper, Stefan K Grebe, Panagiotis Z Anastasiadis, Han W Tun, John A Copland
• Journal: Cancer research (Cancer Res) Vol. 74 Issue 17 Pg. 4796-810 (Sep 01 2014) ISSN: 1538-7445 [Electronic] United States
• PMID: 24962026 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

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

Topics

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