Identification of extracellular matrix metalloproteinase inducer in stromal cells in a spontaneous metastasis model in rats

DONADIO AC; REMEDI MM; FREDE SILVIA; TANG YI; YAN LI

Vallel Hermoso

Congreso; 6. Tango Lessons for Brain Cancer Research. Understanding Cellular Intricacy, Improvising New Therapies; 2007

James McDonnell Foundation

Host-tumor interaction provides a crucial signal in regulating the pericellular proteolysis during tumor invasion. The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) on tumor cells plays an active role in invasion and metastasis through the induction of metalloproteinases expression by adjacent stromal cells, and the consequent modulation of cell-substrate and cell-cell adhesion processes. The present study evaluates the expression of EMMPRIN protein intumor and stromal cells in a spontaneous metastasis model in rats. Moreover, we analyzed the regulation of the EMMPRIN expression by tumor-stromal cell interations in an in-vitro coculture system. Cultured tumor cells (TuE-t cells) develop tumor growth and metastasis mainly in the liver and spleen, when they are injected in the mammary gland fat pad of Wistar rats. Immunohistochemical studies showed EMMPRIN-positive tumor cells in tumor masses as well as in spleen and liver samples from tumor bearing rats. Moreover, liver samples showed metastatic foci and a significant increase in EMMPRIN expression in stromal cells compared with control rats. The spleen, where only scattered tumor cells were present, did not showed significant differences in EMMPRIN expression between tumor bearing and control rats. The increase in EMMPRIN expression in hepatic cells was investigated in a co-culture system. An increase in EMMPRIN expression in Buffalo Rat Liver (BRL) cells co-cultured with tumor cells was demonstrated. This expression could be inhibited by an anti-EMMPRIN antibody, suggesting that EMMPRIN itself was responsible for this induction. Taken together, these results reinforce the idea of stromal participation in the malignancy of tumors, promoting a microenvironment proper for tumor cells anchorage and growth.