EMMPRIN has a role in invasion and
metastasis through the induction of
MMPs and the consequent modulation of cell-substrate and cell-cell adhesion processes. The present study evaluates the expression of
EMMPRIN protein and
MMP-2/9 activity in
tumor and parenchymal cells in a spontaneous
metastasis model in rats. Moreover, we explore the regulation of
EMMPRIN and MMP-9 by
tumor-epithelial cell interactions in vitro. By zymography, we observed an increased
proMMP-9 expression in both metastasized liver and spleen samples from
tumor bearing rats. Immunohistochemical studies showed
EMMPRIN-positive
tumor cells in
tumor biopsies as well as in spleen and liver samples from
tumor bearing rats. Interestingly, a significant increase in
EMMPRIN expression in hepatic cells was also detected. The regulation of
EMMPRIN expression in
tumor and liver cells in response to
tumor-host interaction was investigated in vitro through a tumor cell line culture on extracellular matrix (ECM) molecules or in co-culture with normal rat liver cells (BRL3A cells). No significant changes in
EMMPRIN expression were detected in tumor cells cultured on ECM molecules. On the other hand,
EMMPRIN protein and MMP-9
mRNA expression were induced in BRL3A cells. The increase in
EMMPRIN expression in BRL3A cells was inhibited by an anti-
EMMPRIN antibody. These results reinforce the main role of
EMMPRIN mediating
tumor-host interactions that may evolve new opportunities for therapeutic interventions.