This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mineo, R. Articles by Belfiore, A. Search for Related Content PubMed PubMed Citation Articles by Mineo, R. Articles by Belfiore, A.

Activation of the Hepatocyte Growth Factor (HGF)-Met System in Papillary Thyroid Cancer: Biological Effects of HGF in Thyroid Cancer Cells Depend on Met Expression Levels

Dipartimento di Medicina Interna e di Medicina Specialistica (R.M., A.C., F.F., L.S., S.R., R.V.), Cattedra di Endocrinologia, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy; and Dipartimento di Medicina Sperimentale e Clinica (A.B.), Cattedra di Endocrinologia, Policlinico Mater Domini, University of Catanzaro "Magna Graecia," 88100 Catanzaro, Italy

Address all correspondence and requests for reprints to: Antonino Belfiore, M.D., Dipartimento di Medicina Sperimentale e Clinica, Policlinico Mater Domini, University of Catanzaro "Magna Graecia," via Tommaso Campanella 115, 88100 Catanzaro, Italy. E-mail: belfiore{at}unicz.it.

Met, the receptor for hepatocyte growth factor (HGF), is overexpressed in approximately 90% papillary thyroid carcinomas. To investigate the role of the HGF-Met system in these tumors, we examined HGF and Met expression in a variety of primary cultures, normal or malignant thyroid cells, and tissue specimens and analyzed the different HGF effects (promotion of mitogenesis, branching morphogenesis, and cell motility and invasion). In cancer specimens, HGF was produced at high levels by tumor stromal cells, and Met was constitutively phosphorylated in malignant cells. No HGF production was found in a panel of malignant thyroid cancer cells. Biological effects of HGF were examined in papillary cancer cell cultures with either high or low Met expression. High-Met cells were more sensitive to the growth effect of HGF (ED₅₀ = 3–5 ng/ml and 10–15 ng/ml in high- or low-Met cells, respectively). Moreover, only high-Met cells underwent branching morphogenesis in response to HGF. In contrast, high-Met cells showed a reduced migration. Met down-regulation by small interfering RNAs resulted in enhanced cell migration and abrogation of branching morphogenesis in response to HGF. Conversely, Met overexpression impaired cell migration while favoring branching morphogenesis and cell adherence to substrate. These data suggest that both Met and HGF are overexpressed in papillary thyroid carcinomas, that Met is frequently activated in these carcinomas and may favor tumor growth, and that the abundance of Met expression may differently regulate cell growth, morphogenesis, and migration in response to HGF.

This article has been cited by other articles:

				O. L. Griffith, A. Melck, S. J.M. Jones, and S. M. Wiseman Meta-Analysis and Meta-Review of Thyroid Cancer Gene Expression Profiling Studies Identifies Important Diagnostic Biomarkers J. Clin. Oncol., November 1, 2006; 24(31): 5043 - 5051. [Abstract] [Full Text] [PDF]