ROLE OF INTEGRINS IN THE ATTACHMENT OF METASTATIC FOLLICULAR THYROID-CARCINOMA CELL-LINES TO BONE

One of the principle targets for metastasis of follicular thyroid carc inoma (FTC) is the skeleton. Because no data are available on the role of the integrin adhesion molecule family in the attachment of FTC to bone, we studied the attachment characteristics of three FTC cell line s to bone and the role of integrins. Three cell lines were used from t he same patient, one (FTC-133) from the primary tumor and two (FTC-236 and FTC-238) from metastases. Attachment of FTC cell lines to bone wa s assessed on conditioned medium of an osteoblastic cell line, coated onto plastic, as an in vitro model of bone matrix. The synthetic RGD ( Arg-Gly-Asp) peptide GRGDS impaired attachment of the FTC cell lines t o bone matrix, demonstrating the role of integrins in the attachment o f FTC to bone. Attachment of FTC-133 to bone matrix was blocked comple tely by GRGDS, whereas attachment of FTC-236 and FTC-238 could not be impaired completely. Semiquantitative polymerase chain reaction (PCR) of cDNA from the cell lines indicated stronger expression of alpha(5) integrin mRNA in FTC-133 than in the other cell lines. In line with th is, attachment of FTC-133 to bone matrix could be inhibited almost com pletely by anti alpha(5) and beta(1) integrin antibodies, indicating t he importance of the fibronectin receptor in the attachment of FTC-133 to bone. Binding of FTC-236 and FTC-238 to bone matrix could not be i nhibited completely by anti-integrin antibodies, suggesting an additio nal role of nonintegrin adhesion molecules in the attachment of FTC-23 6 and FTC-238 to bone. The synthetic bone sialoprotein cyclic peptide, CNB, revealed antiadhesive effects in the binding of FTC to bone. In conclusion, integrins play an important role in the attachment of meta static FTC to bone. Differences in the functional involvement of integ rins in the attachment to bone are observed between the three cell lin es studied. From the present results, antiadhesive interventions with synthetic RGD peptides in FTC may be designed.