Different patterns of gelatinolytic activity in pituitary macro- and microadenomas

Gelatinases, Matrix MetalloProteinase(MMP)-2 and MMP-9, belong to zinc-dependent endopeptidases involved in several physiological and pathological processes including inflammation and tumor development. Because the information about the involvement of gelatinases in pituitary adenoma (PA) development are scant, our objective was the analysis of MMP-2 and MMP-9 activity in serum and tumor tissue of PA patients.

Twenty one patients with PA (macroadenoma n=18, microadenoma n=3), qualified to the endoscopic resection of tumors were enrolled. Venous blood samples were collected before the surgery and PA tissue was collected during the surgery. Tissue material was homogenized in a buffer containing 0.1M Tris-HCl pH 7.4 and centrifuged. The supernatant was set to the equal protein content 18μg/sample. Protein level in tissue samples was estimated with Bradford method. MMP-2 and MMP-9 analysis in serum and tissue was performed with gelatin zymography.

The proteolytically activated forms of MMPs were not observed in the analyzed sera. Serum activities of MMP-2 and MMP-9 did not statistically differ between patients with micro and macroadenomas. The analysis of material obtained from tissue of microadenomas showed slightly lower activities of both forms of MMP-9 (pro-MMP-9 and MMP-9/lipokalin heterodimer). Simultaneously the increased activity of pro-MMP-2 in comparison to macroadenomas was observed. Although differences observed did not reach statistical significance, only in the case of microadenomas the presence of the active form of MMP-2 (molecular weight 65kDa band) was observed.

In the course of PA growth the change the biochemical profile of the gelatinolytic activity within the tumor tissue is observed. Initially, the higher activity of MMP-2 in microadenomas and elevated activity of MMP-9 in macroadenomas were detected.