Establishment and Characterization of a Malignant Epithelioid Hemangioendothelioma from Mouse Thyroid Tumor

Abstract

A mouse epithelioid hemangioendothelioma (mEHE) cell line, passagablein vivo without TSH stimulation, was established from a thyroid tumor. Before establishment of the cell line, the primary thyroid tumor which was co-transplanted with a TSH-producing pituitary adenoma showed signs of hyperplasia and then transformed during severalin vivo transplantable passages. The cell line which was established from anin vitro culture, was deficientin thyroid-specific differentiation function and had characteristics of endothelial cell origin such as vascular cavity formation and factor VIII expression. The cell growth of mEHE/CH1-5 cell lines was independent of TSH but was inhibited by c-AMP and vitamin D3. c-Myc proto-oncogene expression was also suppressed by vitamin D3 treatment. Both serum depletion and heparin treatment induced morphological changesin mEHE/CH 5 from an epithelial cell-like to an endothelial cell-like shape. Immunohistochemical analysis showed that epithelial membrane antigen expression was decreased and factor VIII expression was increasedin relation to the morphological changes.in a furtherin vivo transplantation experiment, the histology of the mEHE/CH5 cell tumor had an angiosarcoma-like structure. These results indicate that this cell line established from a thyroid tumor possesses both epithelial and endothelial characteristics. The mEHE/CH5 cells might provide a good model for analyzing thyroid tumorigenesis and allow functional characterization of endothelial cells. © 1995, The Japan Endocrine Society. All rights reserved.