While Wilms tumour—also known as nephroblastoma-- is rare, it is the most prevalent childhood kidney cancer. Researchers at Children’s Hospital Los Angeles have now pinpointed a disruption in early kidney progenitor cell development that can be linked to the formation of Wilms tumour.

In a study published in Advanced Science, researchers at the GOFARR Laboratory in Urology compared kidney progenitor cells from a tumour with precursor cells from a healthy kidney. Normally, these precursor cells mature into kidney cells, but when their early development is dysregulated, they behave like cancer stem cells.

While most children with Wilms tumour are successfully treated, current therapies are aggressive.  A minority of these patients have unfavourable prognoses or relapses; for these children, there is no existing therapy. “By achieving a more precise understanding of how Wilms tumours develop, our goal is to find new treatments for all types of Wilms tumour,” says Laura Perin, PhD, Co-Director of the GOFARR laboratory and senior study co-author with Stefano Da Sacco, PhD, another researcher at the GOFARR Laboratory. 

Instead of developing into kidney cells, they develop into tumour cells

“Pediatric Wilms tumour can be considered a developmental cancer,” says Dr. Perin, who is also an Associate Professor at the Keck School of Medicine of USC. “The normal adult kidney lacks kidney precursor cells, as they are “exhausted” before birth. But in Wilms tumours, instead of giving rise to a functional kidney, these precursor cells persist and form the tumour mass.”

The researchers characterized these Wilms tumour kidney precursor cells, finding that these cells can reproduce the original tumour. “They are aggressive, they’re drug-resistant, they metastasize like cancer cells, and they are able to create the full tumour that we see in patients,” says Astgik Petrosyan, PhD, researcher at the GOFARR Lab and first author of the study. 

Cells that are oblivious to growth signals

The kidney precursor cells that generate Wilms tumours also abnormally expressed ITGβ1 and ITGβ4, proteins that help cells communicate with their microenvironment. “This abnormal attachment to their microenvironment favours the uncontrolled replication of these cells and guides the formation of the tumour mass,” says Dr. Da Sacco.

"Our findings provide a more accurate understanding of the different stages of both normal and abnormal kidney development,” says Dr. Perin. “This can possibly help the diagnosis of Wilms tumour, leading to more effective treatments for these patients.”

Other study co-authors include: Valentina Villania, PhD, of CHLA; Paola Aguiari, PhD, of CHLA and David Geffen School of Medicine at UCLA - VA Healthcare System; Matthew E. Thornton, MS, of the Keck School of Medicine of USC; Yizhou Wang, PhD, and Alex Rajewski, PhD, of Cedars-Sinai Medical Center; Shengmei Zhou, MD, of CHLA, Paolo Cravedi, MD, PhD of the Icahn School of Medicine at Mount Sinai; Brendan H. Grubbs, MD, of the Keck School of Medicine of USC; Roger E. De Filippo, MD, Sargis Sedrakyan, PhD and Kevin V. Lemley, MD, PhD, of CHLA and the Keck School of Medicine at USC; and Marie Csete, MD, PhD of USC.

Source: Children's Hospital Los Angeles