Open AccessExpression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma
Author(s) -
Nakamura Ritsuko,
Oyama Takeru,
Tajiri Ryosuke,
Mizokami Atsushi,
Namiki Mikio,
Nakamoto Masaru,
Ooi Akishi
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12649
Subject(s) - cell migration , cell , gene silencing , cancer cell , microbiology and biotechnology , cell growth , cancer research , biology , cancer , cell culture , gene , genetics
Neural epidermal growth factor‐like like ( NELL ) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL 1 and functions of NELL 2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL 1 and NELL 2 in renal cell carcinoma ( RCC ) using clinical specimens and cell lines. We show that, whereas NELL 1 and NELL 2 proteins are strongly expressed in renal tubules in non‐cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL 1 and NELL 2 mRNA expression was also detected in RCC cell lines. Analysis of NELL 1/2 promoter methylation status indicated that the CpG islands in the NELL 1 and NELL 2 genes are hypermethylated in RCC cell lines. NELL 1 and NELL 2 bind to RCC cells, suggesting that these cells express a receptor for NELL 1 and NELL 2 that can transduce signals. Furthermore, we found that both NELL 1 and NELL 2 inhibit RCC cell migration, and NELL 1 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.