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Laminin Receptors in Differentiated Thyroid Tumors: Restricted Expression of the 67-Kilodalton Laminin Receptor in Follicular Carcinoma Cells¹

Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (G.R.), Dipartimento di Biologia e Patologia Cellulare e Molecolare (N.M., G.R., M.V.), Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica (F.M., S.D.R., G.F.F.), Università Federico II, 80131 Naples, Italy; and the Molecular Pathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health (M.E.S.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Nunzia Montuori, M.D., Dipartimento di Biologia e Patologia Cellulare e Molecolare, via S. Pansini 5, 80131 Naples, Italy. E-mail: mavitale{at}cds.unina.it

The expression of integrin laminin receptors was investigated in normal thyroid primary cultures; immortalized normal thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid tumor cell lines; seven thyroid tumors (four papillary and three follicular carcinomas); and normal thyroid glands. The expression of ₁ß₁, ₂ß₁, ₃ß₁, ₆ß₁, and ₆ß₄ was found in all tumor specimens and in tumor cell lines, whereas normal thyroid cells and TAD-2 cells lacked the expression of ₆ß₄. Despite the presence of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO cells to immobilized laminin-1 was poor, whereas WRO cells and follicular carcinoma-derived cells displayed a strong adhesion. Indeed, WRO and follicular carcinoma-derived cells showed expression of a nonintegrin laminin receptor, the 67-kDa high affinity laminin receptor (67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic adenoma, follicular adenoma, and papillary carcinoma-derived cells did not express the 67LR. Adhesion of WRO and follicular carcinoma-derived cells to laminin-1 was specifically inhibited by a recombinant polypeptide containing laminin-binding domains of 67LR, demonstrating that this receptor confers to follicular carcinoma cells attachment capacity to laminin. Moreover, tissue specimens from follicular carcinomas expressed the 67LR, whereas follicular adenomas and normal thyroid tissues were negative. In thyroid tumors, integrin receptors, although abundant, participate weakly in adhesion to laminin. The expression in follicular carcinoma cells of a functional, high affinity 67LR together with nonfunctional integrin LM receptors could be responsible for the tendency of follicular carcinoma cells to metastasize by mediating stable contacts with basal membranes.

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