Production of basic fibroblast growth factor by human non small cell lung cancer cells

Basic fibroblast growth factor (bFGF), a potent angiogenic cytokine, also acts as autocrine growth factor for certain malignant cells. We investigated the production of bFGF in human NSCLC cell lines (prinlary and metastatic). In 8/10 cell lines bFGF was detected by immunocytochemistry in cytoplasm. Additionally, Western blot analysis confirmed the presence of this protein in cytosol preparations (CP). With ELISA levels of bFGF in CP were in the range of 50–916 pg/mg protein. Specific mRNA for bFGF was demonstrated in 9 out of 10 cell lines by Northern blotting. Heparin-Sepharose fractions of CP stimulated the proliferation of freshly isolated human umbilical vein endothelial cells. This effect could be neutralized by anti-bFGF MoAb. Incubation of cell lines with bFGF-antisense oligonucleotides and pentosan sulfate resulted in a growth inhibition of some, with suramin of all samples tested. Furthermore expression of bFGF was detected by immunohistochemistry in 11/11 NSCLC sections. Our results suggest that endogenous bFGF may be involved in autocrine growth stimulation and/or neoangiogenesis in human NSCLC. Therapies aiming at interruption of this autocrine/paracrine loop may be clinically relevant.