Neutrophils promote the metastatic phenotype of tumors by metalloproteinases and adhesion molecules regulation

REMEDI MM; DONADIO AC; BONACCI GR; CHIABRANDO GA

Córdoba

Congreso; VII Latinamerican Congress of Immunology; 2005

Tumor cells interacts with host cells, extracellular matrix (ECM) and basal membrane by adhesion molecules. Degradation of ECM by proteases plays a key role in tumor invasion and metastasis. We have reported a tumor model by TuE-t cell inoculation into the mammary gland of rats which shows neutrophils (PMN) tumor infiltration and liver-spleen metastasis.To evalulate the PMN influence in tumor invasion and metastasis, we analyzed ICAM, uPAR and MMP2 expression in TuE-t cell culture with conditioned medium (CM) from PMN isolated from normal (CM-N) and bearing tumor rats (CM-BT). Considering relative intensity of fluorescence (RIF) values from flow cytometry, we observed a decreasing of ICAM expression when TuE-t cells were cultured in the presence of 100% CM-BT and 100% CM-N compared to control (0,66±0,30 and 0,90±0,19 vs 1,00 respectively), which was coincident with an increased de-attachment of cells. On the other hand, uPAR expression was not affected. Analysis of culture supernatant of TuE-t cells by zymography and densitometry showed an increased pro-MMP2 activity when these cells were cultured in the presence of CM-BT and CM-N (47±16% vs 16±6%, respectively) respecto to control. In conclusion, PMN soluble mediators induce to decrease the ICAM expression and to increase MMP2 activity in tumor cells, which could favour the cell spreading and invasion in a tumor invasive phenotype.