title: Role of integrins in the attachment of metastatic follicular thyroid carcinoma cell lines to bone.
abstract: One of the principle targets for metastasis of follicular thyroid carcinoma (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 lines to bone and the role of integrins. Three cell lines were used from the 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 was 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 to bone matrix, demonstrating the role of integrins in the attachment of FTC to bone. Attachment of FTC-133 to bone matrix was blocked completely 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 alpha5 integrin mRNA in FTC-133 than in the other cell lines. In line with this, attachment of FTC-133 to bone matrix could be inhibited almost completely by anti alpha5 and beta1 integrin antibodies, indicating the 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 inhibited completely by anti-integrin antibodies, suggesting an additional role of nonintegrin adhesion molecules in the attachment of FTC-236 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 metastatic FTC to bone. Differences in the functional involvement of integrins in the attachment to bone are observed between the three cell lines studied. From the present results, antiadhesive interventions with synthetic RGD peptides in FTC may be designed.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, University Hospital Leiden, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Smit
authors.forename: G
authors.initials: G
authors.lastname: van der Pluijm
authors.forename: H J
authors.initials: HJ
authors.lastname: Vloedgraven
authors.forename: C W
authors.initials: CW
authors.lastname: Löwik
authors.forename: B M
authors.initials: BM
authors.lastname: Goslings
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary; D000328:Adult; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001857:Bone Matrix / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010006:Osteoblasts / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D012795:Sialoglycoproteins; C049554:glycyl-arginyl-glycyl-aspartyl-serine