Trajectory inference analysis pointed to SIX2+CITED1+ as the nephrogenic cancer stem cells at the origin of Wilms tumor.
Investigators at Children’s Hospital Los Angeles have identified a disruption in early renal progenitor cell development that they believe could be linked to the formation of Wilms tumor, the most prevalent pediatric kidney cancer.1,2
The results were published in Advanced Science.
"Our findings provide a more accurate understanding of the different stages of both normal and abnormal kidney development. This can possibly help the diagnosis of Wilms tumor, leading to more effective treatments for these patients,” said senior author Laura Perin, PhD, in a news release on the findings.2 Perin is an associate professor at the Keck School of Medicine at the University of Southern California and the co-director of the GOFARR laboratory in urology at Children’s Hospital Los Angeles.
For the study, progenitor cells expressing SIX2+CITED1+ from a Wilms tumor were compared with precursor cells from a healthy kidney.
The investigators found that expression-level and phenotypic differences of SIX2+CITED1 differentiated Wilms tumor cells from the healthy kidney cells. These differences may prevent normal depletion of progenitor cells.
“Pediatric Wilms tumor can be considered a developmental cancer. The normal adult kidney lacks kidney precursor cells, as they are ‘exhausted’ before birth. But in Wilms tumors, instead of giving rise to a functional kidney, these precursor cells persist and form the tumor mass,” said Perin in the news release.
When the SIX2+CITED1+ cells from the Wilms tumor were injected into immunodeficient mice, they formed xenografts that showed metastatic capabilities, drug-resistance, and the ability to reproduce the original tumor. Additional trajectory inference analysis pointed to SIX2+CITED1+ as the nephrogenic cancer stem cells at the origin of Wilms tumor.
Further, the precursor cells were found to abnormally express ITGβ1 and ITGβ4, which are proteins that allow cells to communicate with their microenvironment. This disruption in specific signaling pathways was found to drive Wilms tumor development.
The authors concluded, “Given the heterogeneity of [Wilms tumor] from sample to sample, we recognized that more studies are needed to characterize [Wilms tumor]fully. Nevertheless, we believe that our extensive transcriptomic studies, together with in vivo and in vitro experiments, might help the development of novel strategies… that could limit cancer development or spread.”
1. Petrosyan A, Villani V, Aguiari P, et al. Identification and characterization of the Wilms tumor cancer stem cell. Adv Sci (Weinh). [published online ahead of print April 28, 2023.] Accessed May 22, 2023. doi:10.1002/advs.202206787.
2. Children’s Hospital Los Angeles researchers uncover new clues to origins of the most common pediatric kidney cancer. News release. Children’s Hospital Los Angeles. May 1, 2023. Accessed May 22, 2023. https://www.newswise.com/articles/children-s-hospital-los-angeles-researchers-uncover-new-clues-to-origins-of-the-most-common-pediatric-kidney-cancer?sc=sphr&xy=10016681