Background: Basic fibroblast growth factor (bFGF) is one of the important angiogenic peptides. Clarification of its localization in human cancer and inflammatory diseases is important for the study of angiogenesis.
Experimental design: Sliced human gastrointestinal carcinomas and inflammatory lesions were frozen after fixation. Immunocytochemical localization of bFGF was studied at the light and electron microscopic levels.
Results: In gastric carcinoma of the diffuse type, bFGF was mainly observed in some of the endothelial cells of the microvasculature and in fibroblasts. Gastric carcinoma of the intestinal type and colonic carcinoma showed the immunoreactivity in fibroblasts, vascular endothelial cells, and in the extracellular matrix (ECM). Carcinoma cells were occasionally positive. In inflammatory lesions, bFGF was most prominent in the ECM. Areas of deposition of bFGF in the ECM partly corresponded to areas of increased immunoreactivity for heparan sulphate proteoglycan. Immunoelectron microscopically, bFGF was localized in the cytosol of fibroblasts and cancer cells but no localization was observed in the lumen of rough endoplasmic reticulum or perinuclear space in any of the cells observed. bFGF was also localized along the luminal surface of vascular endothelial cells, in nuclei of fibroblasts, vascular endothelial cells, smooth muscle cells, and some cancer cells, and in the ECM.
Conclusions: Extensive localization of bFGF in the ECM was related to the areas of increased vascular permeability and active angiogenesis. In cancer tissues, the distribution pattern of bFGF supports a paracrine mechanism among mesenchymal cells rather than a direct paracrine mechanism on vascular cells from carcinoma cells. Nuclear localization of bFGF may support its activity as a transcriptional factor.