Hepatocyte growth factor (HGF) downregulates thrombospondin 1 (TSP-1) expression in thyroid papillary carcinoma cells.
This study investigates the expression of thrombospondin-1 in papillary carcinoma of the thyroid and the role of Met-HGF interaction in TSP-1 regulation. In tissue sections, immunostaining for TSP-1 was associated with the fibrous tumour stroma, and showed areas of marked intensity adjacent to the basal membrane of tumour cells. Investigation of TSP-1 RNA expression showed that, in 10 of 14 cases, TSP-1 mRNA levels were significantly lower in tumour tissue (20-100% reduction; mean = 55% +/- 20; p = 0.001) than in the corresponding normal thyroid. Since it has been reported that HGF can downregulate the expression of TSP-1 mRNA, TSP-1 mRNA levels were measured in 7 primary cultures, established from thyroid papillary carcinomas (TPC), and in 1 TPC cell line prior to, or after, stimulation with HGF. A marked decrease in TSP-1 mRNA levels was observed after HGF stimulation in 6/7 primary cultures (60-100% decrease (mean = 79 +/- 15%; p = 0.006) and in the TPC cell line; moreover, the decrease in TSP-1 mRNA in cell extracts was associated with a decrease in TSP-1 protein in culture supernatants. The HGF activity was dose dependent and the downregulation lasted for at least 48 h after stimulation. The high-level expression of Met protein, the high-affinity receptor for HGF, in most cases of papillary carcinoma of the thyroid is consistent with the possibility that HGF-Met interaction plays a crucial role in regulating the expression of TSP-1 in this tumour type.
Scarpino
Stefania
S
Dipartimento di Diagnostica di Laboratorio e Patologia, Ospedale Sant'Andrea, II Facoltà di Medicina e Chirurgia, Università La Sapienza, Rome, Italy. stefania.scarpino@uniroma1.it
Di Napoli
Arianna
A
Taraboletti
Giulia
G
Cancrini
Antonio
A
Ruco
Luigi P
LP
D000328:Adult; D002291:Carcinoma, Papillary / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019700:Thrombospondin 1; D017228:Hepatocyte Growth Factor