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Cadmium and Lead Decrease Cell-Cell Aggregation and Increase Migration and Invasion in Renca Mouse Renal Cell

Ryan Akin1, David Hannibal1, Margaret Loida1

  • 1Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.

International Journal of Molecular Sciences
|December 19, 2019
PubMed
Summary
This summary is machine-generated.

This study reveals that cadmium and lead exposure promote renal cell carcinoma (RCC) progression by disrupting cell adhesion. These metals enhance tumor cell migration and invasion, highlighting a potential environmental risk factor for metastatic RCC.

Keywords:
E-cadherincadmiuminvasionleadmatrix metalloproteinase-9migrationp120-cateninrenal cell carcinoma

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Area of Science:

  • Toxicology
  • Oncology
  • Cell Biology

Background:

  • Metastatic renal cell carcinoma (RCC) has a poor prognosis, with a 5-year survival rate of approximately 12% for metastatic disease.
  • Elevated blood levels of cadmium and lead have been observed in RCC patients.
  • Disruption of cell-cell adhesion is crucial for epithelial-to-mesenchymal transition and tumor metastasis.

Purpose of the Study:

  • To investigate the impact of cadmium and lead on the progression of renal cell carcinoma (RCC).
  • To assess the effects of these metals on the cadherin/catenin complex in Renca cells, a mouse RCC cell line.

Main Methods:

  • Examined the effects of cadmium and lead on E-cadherin and p120-catenin expression in Renca cells.
  • Measured matrix metalloproteinase-9 (MMP-9) levels.
  • Assessed Renca cell aggregation, wound healing (scratch assay), migration, and invasion.
  • Evaluated the impact of cadmium and lead on the cadherin/catenin complex.

Main Results:

  • Lead induced a concentration-dependent loss of E-cadherin.
  • Cadmium increased p120-catenin expression (isoform 1).
  • Lead significantly increased matrix metalloproteinase-9 levels.
  • Both metals decreased Renca cell aggregation, indicating cadherin/catenin complex disruption.
  • Both metals enhanced wound healing, migration, and invasion.

Conclusions:

  • Cadmium and lead promote renal cell carcinoma (RCC) progression.
  • These metals disrupt homotypic cell-cell adhesion by affecting the cadherin/catenin complex.
  • The findings suggest environmental cadmium and lead exposure as potential risk factors for RCC metastasis.