CD44-hyaluronic acid interaction modulates metalloproteinases in a T cell murine lymphoma and in inflammatory leukocytes

ALANIZ LAURA; CABRERA PAULA; GRECKZANIK SOFÍA; BLANCO GUILLERMO; ALVAREZ ELIDA; HAJOS SILVIA E

La Habana, Cuba

Congreso; 6to Congreso Latinoamericano de Inmunología ALAI; 2002

ALAI

Resumen Matrix metalloproteinases (MMPs) play an important role in leukocyte infiltration, as well as in tumor invasion, due to its ability to degrade extracellular matrix components, such as collagen, elastin and laminin. The aim of this study was to investigate weather CD44-HA interaction modulates expression and activity of metalloproteinases. Two cell lines derived from a T cell lymphoma (LBLa and LBLc) and a murine model of arthritis-like inflammation were used since a causal connection between inflammation and cancer has been proposed. Tumor cell lines were cultured in RPMI free of FCS in the presence or absence of HA during 24 hours and were treated with anti-mouse CD44 IM7 Mab, isotype control or culture medium; supernatants were collected for evaluation by zymography and western blotting. Results showed an increased gelatinolitic activity of LBLa supernatants after incubation with HA. Activity of LBLa supernatants was higher as compared to LBLc, effect was reduced by IM7 Mab treatment. Western blotting confirmed the presence of MMP-2 and MMP-9. The zymosan air-pouch inflammatory model showed a high expression and activity of MMP-2 and MMP-9 in the exudates harvested 40 hours post-injection. This activity was inhibited after 8 hours of treatment with IM7 Mab while isotype Mab and saline were used as controls. Our findings demonstrated that CD44-HA interaction modulated metalloproteinases expression and activity in both models studied. The more aggressive behaviour and metastatic capacity of LBLa tumor cell line compared to LBLc, previously demonstrated correlated with higher gelatinolitic activity induced by HA treatment.