Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

Ritsuko Nakamura* (Corresponding Author), Takeru Oyama, Ryosuke Tajiri, Atsushi Mizokami, Mikio Namiki, Masaru Nakamoto, Akishi Ooi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior.
Original languageEnglish
Pages (from-to)656-664
Number of pages9
JournalCancer Science
Issue number5
Early online date26 Mar 2015
Publication statusPublished - May 2015

Bibliographical note

We thank Professors Michael Rehli, Yoshiaki Ito, and Kristian Helin for gifting plasmids, Dr. Alasdair MacKenzie (University of Aberdeen) for helpful discussion, and Mr. Takashi Mizukami, Ms. Ryoko Tokuda, and Ms. Sanae Funaoka (Kanazawa University) for technical assistance.


  • cell migration
  • methylation
  • NELL1
  • NELL2
  • renal cell carcinoma


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