GELATINASE-B (MMP-9) PRODUCTION AND EXPRESSION BY STROMAL CELLS IN THE NORMAL AND ADULT THYMUS AND EXPERIMENTAL THYMIC LYMPHOMA

Correlative and functional evidence support a crucial role for metallo proteinase (MMP) activity in tumor progression. Dysregulation of MMP p roduction at local tumor sites is thought to participate in the remode ling of the local stromal tissue necessary for tumor growth. The exten t of damages in local tissues is often reflected by the high concentra tion of MMP released in the bloodstream of cancer patients. The integr ity of the thymic architecture plays a crucial role in the development of mature T cells, but it is compromised by extensive remodeling occu rring during the development of thymic lymphomas. In the present work, we have used an experimental thymic lymphoma model to investigate the regulation of MMP-9 (gelatinase B) production in animals bearing larg e thymic lymphomas. We show a 3-fold increase in serum gelatinase B (G el B) levels in animals bearing thymic lymphoma compared with those fo und in normal animals and a correlation between these levels and the s ize of the tumor. Although Gel B was found within the thymic tumor, ly mphoma cells did not express it in vivo, indicating that Gel B express ion was associated with thymic stromal cells rather than lymphoma cell s. This was corroborated by evidence that lymphoma cells have the capa city to stimulate Gel B gene expression in stromal cells. Our results suggest that lymphoma cells can exert a significant control over Gel B expression by local stromal cells, thereby inducing the extensive rem odeling necessary for tumor growth. (C) 1997 Wiley-Liss, Inc.