Role of Growth Factors on Human Parathyroid Adenoma Cell Proliferation

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-beta 1) and their effects have been extensively evaluated in different kinds of endocrine disease. 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 hrTGF beta 1, 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. Cell count (x10000) in the control group was 3.73 +/- A 0.32. Low-dose TGF-beta 1 stimulation resulted in 5.25 +/- A 0.38 cells, and high-dose TGF-beta 1 stimulation resulted in 2.35 +/- A 0.37 cells. IGF-1 stimulation resulted in 5.4 +/- A 0.65 cells, bFGF stimulation in 5.68 +/- A 0.86 cells, and VEGF stimulation resulted in 6.03 +/- A 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 +/- A 4.98% of IGF-1-stimulated cells were found in S-phase compared with 7.55 +/- A 3.2% of control group cells (p < 0.0001). Growth factors seem to play an important role in parathyroid adenoma cell proliferation; IGF-1, bFGF, VEGF, and low-dose TGF-beta 1 promote cell proliferation, whereas high-dose TGF-beta 1 inhibits these phenomena.