Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility

Katja Eloranta; Ruth Nousiainen; Stefano Cairo; Mikko P Pakarinen; David B Wilson; Marjut Pihlajoki; Markku Heikinheimo

doi:10.3389/fped.2021.660482

Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility

Front Pediatr. 2021 Jun 22:9:660482. doi: 10.3389/fped.2021.660482. eCollection 2021.

Authors

Katja Eloranta¹, Ruth Nousiainen¹, Stefano Cairo^{2

3}, Mikko P Pakarinen⁴, David B Wilson^{5

6}, Marjut Pihlajoki¹, Markku Heikinheimo^{1

5}

Affiliations

¹ Pediatric Research Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
² XenTech, Evry, France.
³ Istituto di Ricerca Pediatrica, Padova, Italy.
⁴ Pediatric Surgery, and Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁵ Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, United States.
⁶ Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States.

Abstract

The neuropilins NRP1 and NRP2 are multifunctional glycoproteins that have been implicated in several cancer-related processes including cell survival, migration, and invasion in various tumor types. Here, we examine the role of neuropilins in hepatoblastoma (HB), the most common pediatric liver malignancy. Using a combination of immunohistochemistry, RNA analysis and western blotting, we observed high level expression of NRP1 and NRP2 in 19 of 20 HB specimens and in a majority of human HB cell lines (HUH6 and five cell lines established from patient-derived xenografts) studied but not in normal hepatocytes. Silencing of NRP2 expression in HUH6 and HB-282 HB cells resulted in decreased cell viability, impaired cytoskeleton remodeling, and reduced cell motility, suggesting that NRP2 contributes to the malignant phenotype. We propose that neuropilins warrant further investigation as biomarkers of HB and potential therapeutic targets.

Keywords: cell viability; hepatoblastoma; liver; migration; neuropilin; pediatric cancer.