Authors: Stefania Scarpino¹; Arianna Di Napoli¹; Giulia Taraboletti²; Antonio Cancrini³; Luigi P Ruco¹

Source: The Journal of Pathology, Volume 205, Number 1, January 2005 , pp. 50-56(7)

Publisher: John Wiley & Sons, Ltd.

Abstract:

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. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: thyroid papillary carcinoma; thyroid tumours; thyroid cancer; thrombospondin-1; hepatocyte growth factor; HGF; HGF receptor; Met protein

Document Type: Research article

DOI: http://dx.doi.org/10.1002/path.1675

Affiliations: 1: Dipartimento di Diagnostica di Laboratorio e Patologia, Ospedale Sant'Andrea, II Facoltà di Medicina e Chirurgia, Università ‘La Sapienza’, Rome, Italy 2: Istituto per le Ricerche Farmacologiche Mario Negri, Bergamo, Italy 3: Dipartimento di Chirurgia C, Ospedale Sant'Andrea, II Facoltà di Medicina e Chirurgia, Università ‘La Sapienza’, Rome, Italy

Publication date: 2005-01-01

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