Vascular endotelial growth factors (VEGF C/D) and tissue-related matriz metalloproteinases (MMPs) association with tumor metastasis

DONADIO AC, REMEDI MM, DURAND S, FREDE S, GENTI S; CHIABRANDO G.

Bariloche, Río Negro, Argentina.

Congreso; XXXIX Reunión Científica Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2003

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.

Metastasis stepwise progression involves matrix extracellular porteolytic activity as well as cytolines and growth factors expression, both compromised in cell-cell and cell-matrix interactions. In this work, by using an experimental tumor model developed in our laboratory, we evaluated the gene expression of VEGF-C and VEGF-D as well as the protein level of MMP2 in liver, spleen, lymph nodes and tumor biopsies. In this model the down regulation of the cell adhesion molecules ICAM-1 and uPAR associated with tumor cell spreading to liver, spleen and lymph nodes was demonstrated. Herein, by semiquantitative RT-PCR analysis, we demonstrated that tumor cells were able to express VEGF-C and VEGF-D mRNA in culture and this expression was maintained in tumors derived from these cells. Liver biopsies from bearing tumor rats showed a significant increase in VEGF-C/D mRNA content compared with normal liver samples. The VEGF-C/D mRNA expression observed in spleen and lymph nodes samples did not showed differences between tumor bearing and normal rats. MMP2 proteins were examined by immunohistochemistry on liver, spleen, lymph nodes and tumor biopsies. Tumor, spleen and lymph node samples were MMP2 negative. On the other hand, on liver samples, even though tumor cells were MMP2 negative, a strong MMP2 expression was detected in the hepatocytes. Thus, these results strongly suggest that growth factors and proteases from the stromal milieu participate in tumor cell anchorage.