Papillary carcinoma of the thyroid: evidence for a role for hepatocyte growth factor (HGF) in promoting tumour angiogenesis.
The pattern of vascularization of papillary carcinoma was investigated in tumour sections from 31 cases and in primary cultures from 12 cases. Tumour sections were immunostained for von Willebrand Factor (vWF) to visualize blood vessels; for endothelial-specific nitric-oxide-synthase (EC-NOS), as a marker of endothelial cell activation; and for Ki-67 to evaluate endothelial cell proliferation. It was found that endothelial cells lining venous vessels located in peritumoural fibrous tissue were intensely EC-NOS-positive and occasionally Ki-67-positive. Capillary vessels of tumour papillae were not stained for Ki-67 and were weakly EC-NOS-positive. Primary cultures of papillary carcinoma cells were used as a potential source of factors active on endothelial cells. It was found that thyroid tumour cells contain RNAs for angiopoietin, vascular endothelial growth factor (VEGF), and VEGF-C; moreover, they release large amounts of VEGF into culture supernatants and exert chemotactic activity in vitro for the endothelial cell line SIEC. The ability of papillary carcinoma cells to release angiogenic factors could be stimulated in vitro. Hepatocyte growth factor (HGF; 25 ng/ml) induced a 1.2- to 5-fold increase in the amount of VEGF released by tumour cells and a 1.2- to 4.2-fold increase in the amount of chemotactic activity present in culture supernatants. Met protein, the high affinity HGF-receptor, is overexpressed in a large proportion of cases of papillary carcinoma. These findings are consistent with the possibility that HGF-Met protein interaction is one of the molecular mechanisms promoting the vascularization of papillary carcinoma of the thyroid.
Scarpino
Stefania
S
Dipartimento di Diagnostica di Laboratorio, Ospedale Sant'Andrea, Università La Sapienza, Roma, Italy.
D'Alena
Francesca Cancellario
FC
Di Napoli
Arianna
A
Ballarini
Francesca
F
Prat
Maria
M
Ruco
Luigi P
LP
D000328:Adult; D000818:Animals; D002291:Carcinoma, Papillary / Q000098:blood supply*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002630:Chemotactic Factors / Q000502:physiology; D016228:Endothelial Growth Factors / Q000502:physiology; D004727:Endothelium; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000502:physiology; D012334:RNA, Neoplasm / Q000032:analysis; D013964:Thyroid Neoplasms / Q000098:blood supply*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002630:Chemotactic Factors; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017228:Hepatocyte Growth Factor; D019001:Nitric Oxide Synthase