Páez Pereda M, Ledda M F, Goldberg V, Chervín A, Carrizo G, Molina H, Müller A, Renner U, Podhajcer O, Arzt E, Stalla G K
Department of Endocrinology, Max Planck Institute of Psychiatry, Munich, Germany.
J Clin Endocrinol Metab. 2000 Jan;85(1):263-9. doi: 10.1210/jcem.85.1.6248.
Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. We studied the expression and function of these enzymes in pituitary cells. We observed the activities of MMP-2 and MMP-9 together with expression of membrane-type MMP and tissue inhibitor of metalloproteinase-1 in all types of human pituitary adenomas. We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas. To examine the function of metalloproteinase activity in pituitary cells we used the synthetic MMP inhibitor batimastat. These studies demonstrate that MMPs secreted by pituitary cells can release growth factors anchored to the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. These results define a new additional mechanism for the control of pituitary hormone secretion and indicate new potential therapeutic targets for pituitary adenomas.
除了在肿瘤侵袭和转移过程中对细胞外基质的消化作用外，最近，基质金属蛋白酶（MMPs）还被提出了新的功能。我们研究了这些酶在垂体细胞中的表达和功能。我们观察了MMP-2和MMP-9的活性，以及膜型MMP和金属蛋白酶组织抑制剂-1在所有类型的人垂体腺瘤中的表达。我们发现垂体腺瘤中MMP活性水平出奇地高，而金属蛋白酶组织抑制剂水平低，这表明垂体腺瘤中细胞外基质降解活性很高。为了研究金属蛋白酶活性在垂体细胞中的功能，我们使用了合成的MMP抑制剂batimastat。这些研究表明，垂体细胞分泌的MMPs可以释放锚定在细胞外基质上的生长因子，进而控制垂体细胞的增殖和激素分泌。这些结果确定了一种控制垂体激素分泌的新的额外机制，并指出了垂体腺瘤新的潜在治疗靶点。
