Different FGF‐2 isoform patterns influence drug sensitivity in human melanoma and murine fibroblast cell lines

Abstract

The effect on drug sensitivity of FGF‐2 expression was evaluated in a murine fibroblast (Balb/A31) and in a human melanoma (MC) cell line. Human metastatic melanoma cells, negative for FGF‐2 expression, were transfected in order to express low (18 kDa), high molecular weight (HMW) and all (ALL) isoforms. Clonogenic assay showed that 18 kDa expression was related to chemoresistance to Dacarbazine (DITC), both in 18 kDa and ALL MC cells with respect to the mock transfected cell line. In contrast, the expression of High Molecular Weigth FGF‐2 isoforms alone produced a chemosensitive phenotype, even if compared to that of FGF‐2‐negative clones. Dacarbazine‐resistant clones were obtained following drug selection confirming that resistance was induced by 18 kDa low molecular weight isoform while high molecular weight isoforms produced a sensitive phenotype. Accordingly high molecular weight isoforms were lost and low molecular isoform was gained from DITC resistant ALL and 18 kDa cell line, respectively. Also we failed to obtain resistant clones from HMW cells.Balb/A31 exogenously expressing different human FGF‐2 isoforms were treated with increasing concentration of doxorubicin, cisplatin and 5‐fluorouracyl. Clonogenic survival was evaluated to determine drug resistance. Results showed a highly variable response dependent on both FGF‐2 isoform expression pattern and treatment.Grant: CRF 2003.0808