The kidneys are part of the renal system, which is responsible for removing waste from the body. The kidneys have a primary role in filtering wastes from the blood, while retaining important electrolytes. The renal artery delivers blood to the kidney, where it subdivides into smaller and smaller vessels, a capillary network known as a glomerulus. A glomerulus is encapsulated by Bowman’s capsule, into which fluid from the blood collects and enters the renal tubule. From there, urine is concentrated in a series of tubules that includes the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule. Bowman’s capsule and the tubule system are part of a larger nephron, of which there are hundreds of thousands to millions in a single kidney.
Renal cell carcinoma (RCC) is a type of kidney cancer that develops in the proximal convoluted tubule. RCC encompasses a number of subtypes, including clear cell RCC, papillary RCC, and chromophobe RCC. RCC is largely chemotherapy-resistant, and therefore, surgery has been the main form of treatment. However, in recent years, new targeted therapies have been explored that have had some success against RCC.
Lifeline® provides renal epithelial cells from multiple locations including:
- Renal Medullary Epithelial Cells
- Renal Proximal Tubule Epithelial Cells
- Renal Cortical Epithelial Cells
- Renal Mixed Epithelial Cells
Lifeline® human renal epithelial cells can be used to study both normal kidney biology, as well as kidney diseases, including renal cell carcinoma. All renal cells can be grown in RenaLife® medium, formulated for optimal growth of Lifeline® renal epithelial cells.
New Research in RCC Therapeutics Using Lifeline® Renal Epithelial Cells
In order to survive, cancer cells often develop a resistance to apoptosis; reactivation of sensitivity to apoptosis is one of the strategies being targeted for cancer therapy. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a soluble factor that can selectively induce apoptosis in cancer cells, leaving normal cells unaffected, a desirable characteristic of a cancer therapy. However, cancers can acquire TRAIL resistance, prompting the search for factors that sensitize cancers to TRAIL-inducing apoptosis. In their recent paper, Henrich et al. investigated whether withanolide E, a steroid lactone, could act as a sensitizing agent for TRAIL in renal carcinoma cells. They found that increasing concentrations of withanolide E sensitized renal carcinoma cells to TRAIL-induced apoptosis. In contrast to other mechanisms of TRAIL sensitization, withanolide E likely sensitizes cancer cells to TRAIL by decreasing the levels of cFLIP, an important cellular factor that enables TRAIL-induced apoptosis. Finally, in an in vivo renal carcinoma cell xenograft model, withanolide E treatment in combination with an antibody against the TRAIL death receptor, DR5, decreased tumor volume and increased survival.
The researchers used Lifeline® human renal epithelial cells grown in RenaLife® medium in their study as normal control cells. They found that combined TRAIL and withanolide E treatment had no effects on normal renal epithelial cells, suggesting that withanolide E could be a cancer cell-selective TRAIL sensitizing agent.
Fernández-Gallardo et al. synthesized heterometallic titanium-gold complexes with the goal of developing chemotherapeutic drugs that do not induce resistance or have toxic side effects compared to current clinical chemotherapeutic compounds, including cisplatin. They found that the heterometallic compounds had greater toxicity to renal carcinoma cell lines compared to cisplatin, but were not as toxic to normal Lifeline® human Renal Proximal tubular cells. One of their most promising heterometallic compounds, compound 5, inhibited renal carcinoma cell migration, and in an in vivo xenograft study, decreased tumor size by 67%, suggesting that it has potent anti-tumor activity. The researchers found that compound 5 may exert its growth suppressive activity through reducing thioredoxin reductase activity, a component of the thioredoxin complex, which is critical for maintaining proper cellular redox status. Therefore, this study suggests that heterometallic titanium-gold complexes, such as compound 5, could be successful chemotherapeutic agents against cancer cells that also spare normal cells.
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