Abstract
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.
Highlights
Papillary carcinoma of the thyroid (PTC) is the most common malignant tumor of the thyroid.Mean age of patients is 30–50 years; females are more affected than males (3:1)
Met protein-positive papillary carcinoma cells are highly responsive to hepatocyte growth factor (HGF) which is effective in stimulating tumor cell adhesion, migration, invasiveness and induces the synthesis and release of chemokines and growth factors [3,4]
HGF or agonistic monoclonal antibodies against Met protein stimulate the migratory capacity of PTC cells; they act as chemoattractants for tumor cells in an in vitro invasion assay and induce migration of papillary carcinoma cells through nucleopore filters coated with matrigel [42]
Summary
Papillary carcinoma of the thyroid (PTC) is the most common malignant tumor of the thyroid. In spite of its well-differentiated histology, the tumor is highly invasive. A multifocal involvement of the thyroid gland is present in 18%–22% of the patients. In the last 10 years, evidence has accumulated that over-expression of Met protein is a distinguishing feature of almost every case of well-differentiated papillary carcinoma. Over-expression of Met protein can profoundly affect the tumorigenesis of papillary carcinoma of the thyroid because crucially involved in the control of the “invasive growth”. Met protein-positive papillary carcinoma cells are highly responsive to hepatocyte growth factor (HGF) which is effective in stimulating tumor cell adhesion, migration, invasiveness and induces the synthesis and release of chemokines and growth factors [3,4]
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