Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines

doi:10.1016/S0039-6060(96)80038-9

Surgery

Volume 120, Issue 6, December 1996, Pages 944-947

https://doi.org/10.1016/S0039-6060(96)80038-9 Get rights and content

Background. Vascular endothelial growth factor (VEGF) is a vascular endothelial cell-specific mitogen secreted by some cancer cells and is a major regulator of angiogenesis. Because thyroid-stimulating hormone (TSH) promotes growth and progression of thyroid cancers, we postulated that TSH may increase the production and secretion of VEGF by thyroid cancer cells.

Methods. We examined primary cultures of normal human thyroid (NT 1.0), medullary thyroid cancer (MTC 1.1), and cell lines derived from the papillary (TPC-1), follicular (FTC-133), and Hürthle cell (XTC-1) thyroid cancer. We quantified the concentration of VEGF in conditioned medium by means of enzyme-linked immunosorbent assay.

Results. Cell lines derived from thyroid secrete VEGF. Basal VEGF secretion was similar in normal and thyroid cancer cells, except XTC-1, which has high basal secretion (p<0.01). All thyroid cancer cells secrete significantly more VEGF than normal thyroid cells after TSH (10 mIU/ml) stimulation (p<0.05). TSH stimulated secretion of VEGF in FTC-133 (8.2 ng/dl versus 18.8 ng/dl), TPC-1 (5.5 ng/dl versus 26.9 ng/dl), and MTC 1.1 (5.9 ng/dl versus 13.4 ng/dl) cell lines (p<0.01), but not in NT 1.0 (8.4 ng/dl versus 9.9 ng/dl) and XTC-1 (25.4 ng/dl versus 31.2 ng/dl) cells.

Conclusions. These results suggest that VEGF secretion is constitutively activated in some thyroid cancers and that VEGF secretion is stimulated by TSH; thus TSH may promote growth in some thyroid cancers by stimulating VEGF secretion and angiogenesis.

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^†: Supported in part by the Leonard Rosenman MD fund, the Edwin H. Zeller fund, Mount Zion Health Systems, and the Veterans Affairs Medical Center.

^††: Presented at the Seventeenth Annual Meeting of the American Association of Endocrine Surgeons, Napa, Calif., April 21–23, 1996.

View full text

Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines†,††

J Biol Chem

Biochem Biophys Res Commun

J Biol Chem

J Biol Chem

Biochem Biophys Res Commun

What is the evidence that tumors are angiogenesis dependent?

J Natl Cancer Inst

Consequences of angiogenesis for tumor progression, metastasis and cancer therapy

Anticancer Drugs

Vascular endothelial growth factor is a secreted angiogenic mitogen

Science

Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues

J Clin Invest

Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor

Cancer Res

Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells

Am J Pathol

Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition

Biochem Biophys Acta

Purification and NH₂-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor

Tumor-secreted vascular permeability factor increases cytosolic Ca²⁺ and von Willebrand factor release in human endothelial cells