The occurrence of liver growth factor in hepatoblastoma

Rapid growth of recurrent disseminated tumor and/or metastases can occur in children after incompletely resected, non-pretreated malignant hepatoblastoma (HB). This accelerated tumor growth is observed during the first four postoperative weeks, which is the period of maximal liver regeneration. One key regulator of regeneration, the hepatocyte growth factor (HGF), may be responsible for the induction of tumor growth. We, therefore, investigated levels and sources of HGF in HB patients. With ELISA we measured elevated serum levels (> 1,000 pg/ml) of HGF in 10 of 23 HB patients in comparison with three healthy children (< 610 pg/ml). HGF values of non-pretreated children with HB ranged from 169-10,183 pg/ml (mean 889 pg/ml) while those of patients after primary chemotherapy reached 608-15,000 pg/ml (mean 4,556 pg/ml). An up to fourfold increase of HGF was detected in 10 of 12 children 24-72 hours after liver resection. With immunoenzymatic staining on cryostat sections and cytospin preparations of the tumors we could localize HGF to the fibroblasts of the mesenchymal tumor components. In contrast, its receptor (c-met) was found to be expressed on the epithelial HB cells. Our results indicate that HGF secretion is enhanced after liver resection in children with HB and thus could have a biological function for growth of HGF receptor-expressing tumor cells. The results of immunostaining further suggest that HB is able to produce HGF as its own growth factor in a local paracrine fashion.