FIBROBLAST GROWTH FACTOR-2 FREE FROM EXTRACELLULAR-MATRIX IS INCREASED IN PAPILLARY THYROID CARCINOMAS AND GRAVES THYROIDS

Fibroblast growth factor (FGF)-2 is stored in the extracellular matrix (ECM). We hypothesized that FGF-2 is mobilized from the ECM and binds to receptors on the surface of FGF-2 responsive cells during thyroid enlargement. To test this hypothesis, we estimated levels of FGF-2 fre e from ECM in thyroids by comparing the efficiency of two methods for FGF-2 extraction (low salt and high salt). Because the high salt conce ntration (more than 1.5 M NaCl) is necessary to release FGF-2 from the normal ECM, FGF-2 extracted by low salt is indicative of ECM-free FGF -2. Human papillary thyroid carcinomas, normal part thyroid, and Grave s' thyroid tissues were homogenized separately in an extraction buffer containing either 0 M NaCl (low salt) or 2.0 M NaCl (high salt), and the concentration of FGF-2 in the extracts was measured by enzyme-link ed immunosorbent assay (ELISA). The yields of low and high salt extrac ts of immunoreactive (ir)FGF-2 from papillary carcinomas (low salt: 40 .0 +/- 7.5, high salt: 233 +/- 53 ng/g tissue, mean +/- SE) were signi ficantly higher than those of normal thyroid tissues extracted by the corresponding salt concentration (low salt: 14.6 +/- 1.8, high salt: 1 23 +/- 12 ng/g tissue). On the other hand, the extractable irFGF-2 fro m Graves' thyroid tissues (low salt: 25.2 +/- 2.5, high salt: 135 +/- 24 ng/g tissue) were not significantly different from that of normal t hyroid tissues. However, the ratio of the extractable irFGF from carci nomas and Graves' thyroids by low salt to that by high salt (0 M/2 M r atio = 0.206 +/- 0.051, 0.209 +/- 0.025) were significantly higher tha n that of normal thyroids (0.120 +/- 0.014) (P < 0.05). These results suggest that intratissue ECM-free FGF-2 is increased in papillary thyr oid carcinomas and Graves' thyroid tissues, and therefore a greater am ount of FGF-2 may be available for stimulation of FGF-2 responsive cel ls.