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2015 ; 106
(5
): 656-64
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Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in
human renal cell carcinoma
#MMPMID25726761
Nakamura R
; Oyama T
; Tajiri R
; Mizokami A
; Namiki M
; Nakamoto M
; Ooi A
Cancer Sci
2015[May]; 106
(5
): 656-64
PMID25726761
show ga
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.