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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

Ritsuko Nakamura1, Takeru Oyama1, Ryosuke Tajiri1

  • 1Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Cancer Science
|March 3, 2015
PubMed

Insights

Neural epidermal growth factor-like (NELL) 1 and 2 are downregulated in renal cell carcinoma (RCC). Promoter hypermethylation silences NELL genes, affecting cancer cell migration and adhesion, suggesting a role in RCC progression.

Area of Science:

  • Molecular biology
  • Oncology
  • Biochemistry

Background:

  • Neural epidermal growth factor-like (NELL) 1 and 2 are extracellular glycoproteins.
  • NELL1 is known for osteogenic effects, and NELL2 for neural development.
  • Their roles in cancer, particularly renal cell carcinoma (RCC), are largely unexplored.

Purpose of the Study:

  • To investigate the expression and function of NELL1 and NELL2 in renal cell carcinoma (RCC).
  • To explore the mechanisms underlying NELL gene regulation in RCC.
  • To determine the impact of NELL1 and NELL2 on RCC cell behavior.

Main Methods:

  • Analysis of NELL1 and NELL2 protein and mRNA expression in clinical RCC specimens and cell lines.
  • Assessment of NELL1/2 promoter methylation status in RCC cell lines.
  • Investigation of NELL1/2 binding to RCC cells and their effects on cell migration and adhesion.

Main Results:

  • NELL1 and NELL2 proteins were significantly downregulated in cancerous RCC areas compared to non-cancerous tubules.
  • NELL1 and NELL2 mRNA expression was silenced in RCC cell lines.
  • Hypermethylation of CpG islands in NELL1 and NELL2 genes was observed in RCC cell lines.
  • NELL1 and NELL2 inhibited RCC cell migration, and NELL1 also inhibited cell adhesion.

Conclusions:

  • NELL gene expression is silenced in RCC, likely through promoter hypermethylation.
  • NELL1 and NELL2 play inhibitory roles in RCC cell migration and adhesion.
  • NELL gene silencing contributes to RCC progression by altering cancer cell behavior.
Keywords:
Cell migrationNELL1NELL2methylationrenal cell carcinoma

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