Autocrine inhibition of chemotherapy response in human liver tumor cells by insulin-like growth factor-II.
Insulin-like Growth Factor (IGF)-II is frequently overexpressed in experimental and human hepatocellular carcinomas (HCCs) and has been correlated with increased tumor growth. We have analyzed, whether IGF-II affects chemotherapy response and apoptosis in human liver tumor cells. Three liver tumor cell lines highly expressed IGF-II and supported their growth in an autocrine manner by secreting excessive amounts of IGF-II. Neutralization of IGF-II significantly increased response to the chemotherapeutic agents cisplatin and etoposide especially at lower, cytostatic doses. While blocking of IGF-II did not increase spontaneous cell death in exponentially growing cultures, increased cell death was found under conditions of confluent growth and chemotherapy. Thus in HCC cells, IGF-II is a relevant protumorigenic growth factor that significantly reduces susceptibility to apoptosis and chemotherapeutic treatment. Therefore interference with IGF-II activity may improve response of HCCs to otherwise inefficient chemotherapeutic agents.
Lund
Per
P
Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, Cologne D-50931, Germany.
Schubert
Dominic
D
Niketeghad
Fataneh
F
Schirmacher
Peter
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019898:Autocrine Communication; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007335:Insulin-Like Growth Factor II; D005047:Etoposide; D002945:Cisplatin