F. Aoudjit et al., GELATINASE-B (MMP-9) PRODUCTION AND EXPRESSION BY STROMAL CELLS IN THE NORMAL AND ADULT THYMUS AND EXPERIMENTAL THYMIC LYMPHOMA, International journal of cancer, 71(1), 1997, pp. 71-78
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.