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Hepatocyte Growth Factor/C-Met Axis in Thyroid Cancer: From Diagnostic Biomarker to Therapeutic Target

View Article: PubMed Central - PubMed

ABSTRACT

The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. This may be relevant for iodine-refractory cancers, the treatment of which is still a major challenge. With this in mind, HGF/c-met expression in thyroid cancer tissue may be useful for prognostic and therapeutic stratification of patients.

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Immunoreactions of hepatocyte growth factor (HGF) in cases of benign colloid goitre and papillary thyroid carcinoma (PTC). (A) Unstained HGF follicular thyroid cells (grey arrow) and HGF stain located on membrane and cytoplasm of stromal cells (black arrow) surrounding thyrocytes, respectively (original magnification ×400). (B) HGF cytoplasmic and membranous immunostaining in PTC follicular cells (black arrow) and unstained HGF stromal cells (grey arrow), respectively (original magnification ×400).
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f2-10.1177_1177271917701126: Immunoreactions of hepatocyte growth factor (HGF) in cases of benign colloid goitre and papillary thyroid carcinoma (PTC). (A) Unstained HGF follicular thyroid cells (grey arrow) and HGF stain located on membrane and cytoplasm of stromal cells (black arrow) surrounding thyrocytes, respectively (original magnification ×400). (B) HGF cytoplasmic and membranous immunostaining in PTC follicular cells (black arrow) and unstained HGF stromal cells (grey arrow), respectively (original magnification ×400).

Mentions: Similar to other tumours,27–29 the cornerstone evidence supporting HGF and c-met utility in the diagnosis of thyroid malignant lesions is built on evidence of specific cellular localizations for each member of the HGF/c-met axis. When thyroid benign lesions shift towards malignancy, the HGF/c-met cellular disposition is dysregulated to the extent that abnormal epithelial cells can simultaneously express the ligand and the receptor.21,24 Among thyroid cancers, papillary thyroid carcinoma (PTC) is associated with marked overexpression (up to 100-fold) of HGF/c-met, which, instead, is rarely expressed in other histotypes, such as follicular, anaplastic, and/or medullary thyroid cancer (Figure 2). Overexpression of HGF/c-met has been found in 75% to 100% of PTC, regardless of the histological variants30–33 (Table 1). Our group has also correlated the expression of HGF/c-met with that of STAT3, which is known to mediate morphogenetic effects, suggesting that this autocrine pathway may be relevant for the establishment of the papillary phenotype.34


Hepatocyte Growth Factor/C-Met Axis in Thyroid Cancer: From Diagnostic Biomarker to Therapeutic Target
Immunoreactions of hepatocyte growth factor (HGF) in cases of benign colloid goitre and papillary thyroid carcinoma (PTC). (A) Unstained HGF follicular thyroid cells (grey arrow) and HGF stain located on membrane and cytoplasm of stromal cells (black arrow) surrounding thyrocytes, respectively (original magnification ×400). (B) HGF cytoplasmic and membranous immunostaining in PTC follicular cells (black arrow) and unstained HGF stromal cells (grey arrow), respectively (original magnification ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5391983&req=5

f2-10.1177_1177271917701126: Immunoreactions of hepatocyte growth factor (HGF) in cases of benign colloid goitre and papillary thyroid carcinoma (PTC). (A) Unstained HGF follicular thyroid cells (grey arrow) and HGF stain located on membrane and cytoplasm of stromal cells (black arrow) surrounding thyrocytes, respectively (original magnification ×400). (B) HGF cytoplasmic and membranous immunostaining in PTC follicular cells (black arrow) and unstained HGF stromal cells (grey arrow), respectively (original magnification ×400).
Mentions: Similar to other tumours,27–29 the cornerstone evidence supporting HGF and c-met utility in the diagnosis of thyroid malignant lesions is built on evidence of specific cellular localizations for each member of the HGF/c-met axis. When thyroid benign lesions shift towards malignancy, the HGF/c-met cellular disposition is dysregulated to the extent that abnormal epithelial cells can simultaneously express the ligand and the receptor.21,24 Among thyroid cancers, papillary thyroid carcinoma (PTC) is associated with marked overexpression (up to 100-fold) of HGF/c-met, which, instead, is rarely expressed in other histotypes, such as follicular, anaplastic, and/or medullary thyroid cancer (Figure 2). Overexpression of HGF/c-met has been found in 75% to 100% of PTC, regardless of the histological variants30–33 (Table 1). Our group has also correlated the expression of HGF/c-met with that of STAT3, which is known to mediate morphogenetic effects, suggesting that this autocrine pathway may be relevant for the establishment of the papillary phenotype.34

View Article: PubMed Central - PubMed

ABSTRACT

The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. This may be relevant for iodine-refractory cancers, the treatment of which is still a major challenge. With this in mind, HGF/c-met expression in thyroid cancer tissue may be useful for prognostic and therapeutic stratification of patients.

No MeSH data available.


Related in: MedlinePlus