Increase of metalloproteinases (MMPs) activity and migratory ability of thyroid tumor cells induced by tumor cell-fibroblast interaction.

DELLA VEDOVA AB; REMEDI MM; GILARDONI MB; MASINI-REPISO AM; PELLIZAS CG; DONADÍO, AC

Florianópolis

Congreso; XV Congress of the Latin American Thyroid Society (LATS); 2013

Latin American Thyroid Society (LATS)

Background: Carcinomas comprise tumor and stromal cells like fibroblasts (Fb), immune and endothelial cells, immersed in the extracellular matrix (ECM).Tumor-stroma cross-talk influences tumor behaviour. Proteases like MMPs induce ECM degradation, genomic instability and epithelial-mesenchymal transition. Fb confer growth-promoting advantage to thyroid carcinoma cells. However, the role of thyroid tumor-Fb interaction in the invasive and migratory ability of tumor cells remain unknown. Objetives: To analyse MMPs expression and thyroid tumor cell migration induced by tumor-Fb interaction. Methods: Thyroid carcinoma papillary (TPC-1), anaplastic (8505) and normal thyroid (N-ThyOri) cell lines were cultured in the presence (co-cultured) or absence of normal Fb. MMP2/MMP9 expression was analyzed in culture supernatants (Conditioned-Media, CMs) by zymography and in cultured cells by immunofluorescence. Tumor cell migration, induced by CMs incubation, was evaluated by the wound healing assay and the presence of lamellipodia/filopodia, as a signal of migratory phenotype, by rhodamine-phalloidin staining. Results: An increase in MMP2 and MMP9 expression alongside with higher levels of active MMP2 was observed in CMs from TPC-1-Fb and 8505-Fb co-cultures. MMP9 protein staining increased in Fb co-cultured with tumor cells while MMP2 displayed a dotted pattern in Fb plasmatic membrane. No significant MMPs changes were observed in N-ThyOri-Fb co-cultures TPC-1 and 8505 cells with lamellipodia/filopodia increased significantly after Fb CMs as well as 8505 cells after tumor-Fb-CMs incubation. A significant wound healing closure was observed only with 8505 cells, after incubation with Fb or 8505-Fb CMs (p≤0.05, Kruskall-Wallis test). Conclusions: Tumor cell-Fb interaction increased MMP2/MMP9 expression and activity. Fb soluble factors could be relevant for the promotion of thyroid tumor cell invasive phenotypes.