An Extracellular Matrix Molecule, Secreted by the Epithelial-Mesenchymal Transition is Associated With Lymph Node Metastasis of Thyroid Papillary Carcinoma

Abstract

Background:Papillary thyroid carcinoma often has lymph node metastasis, compared with follicular thyroid carcinoma. The study showed that epithelial-mesenchymal transition occurs in carcinoma cells during the first stage of metastasis, where some extracellular matrix molecules are secreted in large quantities. Sialic acid carried by fibronectin as the antigen of the monoclonal antibody (MoAb) JT-95, was detected in 90% of papillary thyroid carcinoma cases, and in a few follicular thyroid carcinomas, in the extracellular matrix of thyroid carcinoma cells.Objectives:The current study was conducted to investigate the association between increasing the number of extracellular matrix molecules, fibronectin, and lymph node metastasis. We also co-cultured a thyroid carcinoma cell line and lymphocyte cell line, with and without MoAb JT-95, in order to investigate the mechanism of cell to cell interaction.Patients and Methods:Immunostaining with JT-95 was performed in 45 papillary thyroid carcinoma cases, and 20 follicular type tumors, to investigate the association between the quantity of fibronectin expression and the frequency of lymph node metastasis. The thyroid carcinoma cell line (SW1736), which secreted fibronectin, and the B cell-lymphoma cell line (Daudi), which held integrin on the cell surface, were co-cultured to observe the adhesion of cells to each other. The SW1736 cell line, pretreated with JT-95, was also co-cultured with the Daudi cell line.Results:There were 39 cases with lymph node metastasis in 59 malignant tumors, and 0 cases in 6 benign follicular type tumors. The staining scores by JT-95 of the 39 tumors with lymph node metastasis were 5+ in eight cases and 6+ in 31 cases. On the other hand, the scores of 20 malignant tumors without lymph node metastasis were < 4+ in all of the cases. In the co-cultured assay, numerous adhesions were observed between the SW1736 and Daudi cells. In contrast, the inhibition of adherences was observed in proportion to the concentrations of JT-95.Conclusions:Increased fibronectin expression in thyroid malignancies is correlated with lymph node metastasis.