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The Pathogenetic Role of the HGF/c-Met System in Papillary Carcinoma of the Thyroid

Department of Clinical and Molecular Medicine, Pathology Unit, Sant'Andrea Hospital, Sapienza University, 00189 Rome, Italy
Author to whom correspondence should be addressed.
Biomedicines 2014, 2(4), 263-274;
Received: 12 September 2014 / Revised: 6 October 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
(This article belongs to the Special Issue New aspects of the Hepatocyte Growth Factor/c-Met System)
The MET oncogene encodes for Met protein, a trans-membrane tyrosine kinase identified as the high affinity receptor for hepatocyte growth factor (HGF). Immunohistochemical studies have demonstrated that Met protein is intensely expressed in tumor cells of >95% cases of thyroid papillary carcinoma. High density of Met protein in tumor cells is the result of increased transcription of a normal MET gene, probably due to a combination of intracellular and extracellular signals. Over-expression of Met protein is more pronounced at the invading front of the tumor and can profoundly affect the tumorigenesis of papillary carcinoma of the thyroid. In fact, Met protein-positive papillary carcinoma cells are highly responsive to hepatocyte growth factor (HGF), which is effective in stimulating tumor cell adhesion, migration and invasiveness. In addition, HGF stimulation of papillary carcinoma of the thyroid (PTC) cells causes up-regulation of COX-2 and down-regulation of CD82/KAI-1; both these molecules have a major role in controlling tumor cell invasiveness. Finally, HGF stimulation of tumor cells may significantly affect the tumor microenvironment. In fact, HGF induces tumor cells to release chemokines active in the recruitment of dendritic cells, and is involved in regulating the production of proangiogenic factors. View Full-Text
Keywords: HGF/Met; Papillary carcinoma; thyroid HGF/Met; Papillary carcinoma; thyroid
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Ruco, L.; Scarpino, S. The Pathogenetic Role of the HGF/c-Met System in Papillary Carcinoma of the Thyroid. Biomedicines 2014, 2, 263-274.

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