Expression and secretion of endostatin in thyroid cancer.
BACKGROUND
In thyroid cancer (TC) endostatin was identified as a powerful negative regulator of tumor angiogenesis in vitro. It is currently being evaluated in phase I trials for antiangiogenic therapy in various solid tumors. The aim of this study was to evaluate endostatin expression in archival TC specimens and its secretion following stimulation with thyrotropin (TSH) and epidermal growth factor (EGF) in TC cell lines.


METHODS
Tissue microarrays of 44 differentiated and 7 anaplastic TC and their metastasis were immunostained for endostatin protein expression and compared with corresponding non-neoplastic thyroid tissue (NT). In vitro, six differentiated (FTC133, FTC236, HTC, HTC-TSHr, XTC, and TPC1) and three anaplastic (C643, Hth74, Kat4.0) TC cell lines were evaluated for basal as well as TSH (1-100 mU/ml) and EGF stimulated (1-100 ng/ml) endostatin.


RESULTS
Endostatin was detected in all TC and more than half of the NT. Endostatin expression was more frequent and intense in differentiated as compared to anaplastic TC. In vitro, basal endostatin secretion varied between 33 +/- 5 pg/ml (FTC236) and 549 +/- 65 pg/ml (TPC1) and was doubled in FTC, when the "primary" (FTC133) was compared with the metastasis (FTC236). Some cell lines showed TSH-induced (e.g., 60% in XTC) or EGF-induced (e.g., 120% in TPC1) upregulation of endostatin secretion, while others did not, despite documented receptor expression.


CONCLUSIONS
This study demonstrates endostatin expression in TC, metastasis and--less frequently and intensely--in NT, suggesting a possible association to tumor progression. In vitro, endostatin secretion of some cell lines is regulated by TSH and EGF, however the individual differences deserve further functional studies. These results support rather tumor-specific than histotype-specific expression and regulation of endostatin in TC.
Hoffmann
Sebastian
S
Department of Surgery, Philipps-University Marburg, Marburg, Baldingerstrasse, Germany. hoffmans@med.uni-marburg.de
Wunderlich
Annette
A
Lingelbach
Susanne
S
Musholt
Petra B
PB
Musholt
Thomas J
TJ
von Wasielewski
Reinhard
R
Zielke
Andreas
A
D018263:Adenocarcinoma, Follicular / Q000378:metabolism* / Q000556:secondary; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary; D002454:Cell Differentiation / Q000187:drug effects; D043169:Endostatins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D016612:Paraffin Embedding; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D004815:Epidermal Growth Factor; D013972:Thyrotropin