Faculty Collaboration Database

Recombinant leukemia inhibitory factor suppresses human medullary thyroid carcinoma cell line xenografts in mice. Cancer Lett 2013 Oct 01;339(1):144-51

Date

07/17/2013

Pubmed ID

23856028

Pubmed Central ID

PMC3771534

DOI

10.1016/j.canlet.2013.07.006

Scopus ID

2-s2.0-84883464713 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Medullary thyroid carcinoma (MTC) is a neoplasm of the endocrine system, which originates from parafollicular C-cells of the thyroid gland. For MTC therapy, the Food and Drug Administration recently approved vandetanib and cabozantinib, multi-kinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Previously, we reported that expression of activated Ras or Raf in the human MTC cell lines, TT and MZ-CRC-1, can induce growth arrest and RET downregulation via a leukemia inhibitory factor (LIF)-mediated autocrine/paracrine loop. In this study, we aimed to evaluate bacterially-produced recombinant human LIF for its efficacy to suppress human MTC xenografts in mice. Here, we report that, consistent with its effects in vitro, locally or systemically administered recombinant LIF effectively suppressed growth of TT and MZ-CRC-1 xenografts in mice. Further, as predicted from its effects in TT and MZ-CRC-1 cell cultures in vitro, recombinant LIF activated the JAK/STAT pathway and downregulated RET and E2F1 expression in tumors in mice. These results suggest that LIF is a potent cytostatic agent for MTC cells, which regulates unique mechanisms that are not targeted by currently available therapeutic agents.

Author List

Starenki D, Singh NK, Jensen DR, Peterson FC, Park JI

Authors

Jong-In Park PhD Professor in the Biochemistry department at Medical College of Wisconsin
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Carcinoma, Neuroendocrine
Cell Line, Tumor
Disease Models, Animal
E2F1 Transcription Factor
Female
Humans
Janus Kinases
Leukemia Inhibitory Factor
Mice
Proto-Oncogene Proteins c-ret
Recombinant Proteins
STAT Transcription Factors
Signal Transduction
Thyroid Neoplasms
Tumor Burden
Xenograft Model Antitumor Assays