Role of growth factors on human parathyroid adenoma cell proliferation.

INTRODUCTION

Primary hyperparathyroidism (pHPT) is caused by a single monoclonal adenoma in more than 80% of patients. Biomolecular mechanisms causing pHPT are still not completely known, even if a great amount of studies have been developed recently, mainly regarding angiogenesis and growth factors. Among the latter, insulin-like growth factor 1 (IGF-1), basic fibroblastic growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta 1 (TGF-beta1) and their effects have been extensively evaluated in different kinds of endocrine disease.

METHODS

Parathyroid cell cultures were prepared from six human adenomatous parathyroid glands that were surgically removed. After 7 days of culture, the cells were refed with DMEM supplemented with 2% FCS alone (control group), or containing hrTGFbeta1, or hrIGF-I, or hrbFGF, or hrVEGF. Then, after 48-hour incubation, cell count was performed by a particle count and size analyzer, and prevalence of cell cycle was analyzed by using a flow cytometer.

RESULTS

Cell count (x10000) in the control group was 3.73 +/- 0.32. Low-dose TGF-beta1 stimulation resulted in 5.25 +/- 0.38 cells, and high-dose TGF-beta1 stimulation resulted in 2.35 +/- 0.37 cells. IGF-1 stimulation resulted in 5.4 +/- 0.65 cells, bFGF stimulation in 5.68 +/- 0.86 cells, and VEGF stimulation resulted in 6.03 +/- 1.03 cells. Statistical analysis revealed significant differences in the control group compared with the growth factor-stimulated groups. Cytometry showed different results in the percentage of cells in S-phase, in particular 22.65 +/- 4.98% of IGF-1-stimulated cells were found in S-phase compared with 7.55 +/- 3.2% of control group cells (p < 0.0001).

CONCLUSIONS

Growth factors seem to play an important role in parathyroid adenoma cell proliferation; IGF-1, bFGF, VEGF, and low-dose TGF-beta1 promote cell proliferation, whereas high-dose TGF-beta1 inhibits these phenomena.