Factor it in: A new approach to modeling the pediatric cancer, Wilms tumor, in culture

Authors

• HM Wojcik
• AO Perantoni

Abstract

Wilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer, affecting 1 in 10,000 children, and represents 6-7% of all cancers under age 15. Most WT cases display a “favorable” triphasic histology, comprised of blastemal, stromal, and epithelial cell types; however, 5-8% of cases are anaplastic or predominantly blastemal, which have a worse prognosis. WT blastemal cells are akin to nephron progenitor cells (NPCs), which arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney, and similarly express SIX2. Blastemal cells are thought to comprise the cancer stem cells (CSCs) in WT, which also express ALDH1 and NCAM. Xenotransplantion of these tumors is the only dependable method to propagate tumor tissue for research or therapeutic screening, as efforts to culture tumors in vitro have invariably failed. Therefore, there is a critical need for better methods for propagating WT stem cells which are amenable to high throughput drug screening and real time testing. Previously, our lab developed niche conditions that support the propagation of murine NPCs in culture. By applying similar conditions to WTs, we have successfully expanded and passaged WT cells that maintain key NPC “stemness” markers, such as SIX2, NCAM and PAX2, suggesting that said conditions are selective for the blastemal population as observed with NPCs. Thus, we have developed a multi-passage in vitro model for studying the blastemal lineage/CSCs in WTs. This system also supports a heterogenous cell population common in WT, upon which potential drug therapies could be tested.

Scientific Focus Area: Cancer Biology

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