Abstract
Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially amoung the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (β1–4, β7,α1–6, αV, αIIb, αL, αM, αX) and of four IRM heterodimers (α2β1, α5β1, αVβ3, αVβ5), was analyzed by fluorescent- activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins α2, α3, α5, β1, β3 and low levels of α1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by α5 and β1. ATC mainly displayed integrins α2, α3, α5, α6, β1 and low levels of α1, α4 and αV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exeptions, namely α4, α6, and β3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of thyroid tumor cell lines to ECM may not be associated with altered IRM expression.
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