The effect of lead on Renal cell carcinoma progression

Abstract

Renal cell carcinoma (RCC) incidence has been steadily increasing over the past few decades, and has become the ninth most common cancer in the United States. It has the highest mortality rate of the genitourinary cancers, with prognosis being heavily reliant on the state of metastasis upon diagnosis. Survival percentage drops drastically with each stage of metastasis, making understanding the mechanisms by which RCC metastasizes vitally important. Previous work in our lab has shown that lead reduces E-cadherin expression and cell-cell aggregation in Renca cells in vitro. The goal of this current research was to investigate how direct and systemic exposure to lead caused Renca cells to change in vivo. Cells that had been previously exposed to lead in vitro were implanted subcutaneously in Balb/c mice and allowed to grow into tumors. Male mice in this condition had significantly larger tumors than controls, and had significant reductions in E-cadherin and beta catenin expression. To investigate systemic exposure, mice were given 30 ppm lead (II) acetate in their drinking water for 20 weeks prior to Renca cell implantation, and then tumors were allowed to seed and grow for 3 weeks. Male mice in this condition also had significantly larger tumors compared to controls, however significant loss of protein expression was not seen. In both direct and systemic exposures, female mice did not exhibit significant differences between lead and control conditions. The results of this research suggest that while lead has a pro-tumorigenic effect when exposed directly to Renca cells, a low dose of lead systemically does not by itself reduce expression of key proteins. Metabolic handling of lead and differences in hormonal landscapes are likely the differentiating factor between male and female mice that contributed to lead-related tumor growth in males but not females.