Integrin alpha V beta 3-dependent thyroid hormone effects on tumour proliferation and vascularisation

Schmohl, Kathrin A.; Han, Yang; Tutter, Mariella; Schwenk, Nathalie; Sarker, Rim S. J.; Steiger, Katja; Ziegler, Sibylle; Bartenstein, Peter; Nelson, Peter J. und Spitzweg, Christine (2020): Integrin alpha V beta 3-dependent thyroid hormone effects on tumour proliferation and vascularisation. In: Endocrine-Related Cancer, Bd. 27, Nr. 12: S. 685-697

Abstract

Thyroid hormones are emerging as critical regulators of tumour growth and progression. To assess the contribution of thyroid hormone signalling via integrin alpha v beta 3, expressed on many tumour cells, endothelial cells, and stromal cells, to tumour growth, we compared the effects of thyroid hormones vs tetrac, a specific inhibitor of thyroid hormone action at integrin alpha v beta 3, in two murine xenograft tumour models with and without integrin alpha v beta 3 expression. Integrin alpha v beta 3-positive human anaplastic thyroid cancer cells SW1736 and integrin alpha v beta 3-negative human hepatocellular carcinoma cells HuH7 were injected into the flanks of nude mice. Tumour growth was monitored in euthyroid, hyperthyroid, hypothyroid, and euthyroid tetrac-treated mice. In SW1736 xenografts, hyperthyroidism led to a significantly increased tumour growth resulting in a decreased survival compared to euthyroid mice, while tumour growth was significantly reduced and, hence, survival prolonged in hypothyroid and tetrac-treated mice. Both proliferation and vascularisation, as determined by Ki67 and CD31 immunofluorescence staining, respectively, were significantly increased in tumours from hyperthyroid mice as compared to hypothyroid and tetrac-treated mice. No differences in tumour growth, survival, or Ki67 staining were observed between the different groups in integrin alpha v beta 3-negative HuH7 xenografts. Vascularisation, however, was significantly decreased in hypothyroid and tetrac-treated mice compared to euthyroid and hyperthyroid mice. Apoptosis was not affected in either tumour model, nor were cell proliferation or apoptosis in vitro. Tumour growth regulation by thyroid hormones in alpha v beta 3-positive tumours has important implications for cancer patients, especially those with thyroid dysfunctions and thyroid cancer patients treated with thyrotropin-suppressive L-thyroxine doses.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1351-0088
• Sprache: Englisch