Extracellular matrix components regulate ACTH production and proliferationin corticotroph tumor cells

The extracellular matrix (ECM) conveys signals through membrane receptors c alled integrins producing changes in cell morphology, proliferation, differ entiation and apoptosis. Previous studies suggest that the ECM plays an imp ortant role in pituitary physiology and tumorigenesis. In the present work we studied for the first time the effects of fibronectin, laminin, collagen I and collagen IV on hormone secretion and cell proliferation in the corti cotroph tumor cell line AtT-20 and in normal pituitary cells, examining the signal transduction mechanisms that mediate these effects. ACTH production in AtT-20 cells was inhibited by fibronectin, laminin and collagen I. A re porter construct with the POMC promoter showed similar results, indicating that the effects of the ECM take place at the level of POMC gene transcript ion. In contrast, ACTH production was not significantly altered in normal p ituitary cells. AtT-20 cell proliferation was stimulated by collagen IV and fibronectin, but inhibited by collagen I and laminin. In parallel, the cel l morphology was modified by the ECM. We found that the production of react ive oxygen species mediate the effects of laminin-and collagen IV. On the o ther hand, the effect of fibronectin was mimicked by beta1-integrin and Rho activation. These results show for the first time that the ECM controls AC TH biosynthesis and proliferation in corticotroph tumor cells and suggest a role for the ECM in corticotroph adenoma development. (C) 2001 Elsevier Sc ience Ireland Ltd. All rights reserved.