The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival
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Read the article on jpedsurg.org ↗Article · Mar 2019 · 1 min read
In brief
In brief
Study demonstrates PIM3 kinase overexpression increases hepatoblastoma tumor growth and cancer stem cell characteristics in cell lines and patient-derived xenografts. Strong PIM3 expression correlates with decreased patient survival, suggesting potential as both a prognostic biomarker and therapeutic target in this most common pediatric liver malignancy.
Written by the GCMD Library team from the article.
Purpose
Hepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival.
Methods
The hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed.
Results
PIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival.
Conclusions
PIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.