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World Journal of Surgery

Published in:

01-09-2011

Osteoprotegerin (OPG) and Related Proteins (RANK, RANKL and TRAIL) in Thyroid Disease

Authors: Sumit K. Sood, Sabapathy Balasubramanian, Sue Higham, Malee Fernando, Barney Harrison

Published in: World Journal of Surgery | Issue 9/2011

Abstract

Background

Osteoprotegerin (OPG), receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and TNF related apoptosis inducing ligand (TRAIL) are the key proteins in the development of bone metastases. Osteoprotegerin improves tumor cell survival and inhibits TRAIL induced apoptosis of cancer cell lines. It also binds to RANKL and inhibits its interaction with RANK (cell surface receptor), which influences osteoclast formation and function. The aim of the present study was to characterize the expression of OPG, RANK, RANKL, and TRAIL in benign and malignant thyroid tissue and thyroid cell lines.

Methods

Archived thyroid tissue from 79 patients (60 differentiated thyroid cancers and 19 benign thyroids) was stained for OPG, RANK, RANKL, and TRAIL by immunohistochemistry. Staining was assessed semiquantitatively and correlated with pathology. Western blots were performed on three human thyroid cell lines: Nthy-ori 3-1 (thyroid follicular epithelium), FTC-133 (follicular thyroid carcinoma), and K1E7 (subclone of papillary thyroid carcinoma).

Results

Osteoprotegerin and RANKL staining was cytoplasmic; RANK staining was nuclear; and TRAIL staining was predominantly cytoplasmic. All four proteins were expressed in benign and malignant tissue. There was significant difference in RANK expression between malignant and benign tissue (8 vs. 84%, respectively; Fisher’s exact test; P < 0.001). RANKL expression was significantly increased in malignant tissue (Fisher’s exact test; P = 0.04). Western blotting showed OPG expression in all cell lines and TRAIL in none. RANK and RANKL were not detected in papillary and follicular cell lines, respectively.

Conclusions

Nuclear expression of RANK protein in thyroid tissue is paradoxical; it could be due to nuclear migration after ligand binding. Suppression of RANK and increased expression of RANKL in malignant tissue warrant further investigation.

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Title: Osteoprotegerin (OPG) and Related Proteins (RANK, RANKL and TRAIL) in Thyroid Disease
Authors: Sumit K. Sood
Sabapathy Balasubramanian
Sue Higham
Malee Fernando
Barney Harrison
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 9/2011
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-011-1185-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Osteoprotegerin (OPG) and Related Proteins (RANK, RANKL and TRAIL) in Thyroid Disease

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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