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INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes
Sabine Hombach-Klonisch1, Cuong Hoang-Vu, Astrid Kehlen
1Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, 06097 Halle, Germany.
International Journal of Oncology
|April 10, 2003
Summary
Insulin-like hormone INSL-3 is newly found in thyroid tumors. Its isoforms are elevated in hyperplastic and cancerous thyroid cells, suggesting potential as new diagnostic markers.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Insulin-like hormone INSL-3 (also known as relaxin-like factor or Leydig-derived insulin-like peptide) is typically found in reproductive tissues and serves as a marker for Leydig cell differentiation.
- Previous research indicated INSL-3's differential expression in neoplastic Leydig and mammary cells, hinting at its role in tumor biology.
- The INSL-3 receptor, LGR8, is expressed in the human thyroid gland, suggesting a potential role for INSL-3 in thyroid function.
Purpose of the Study:
- To investigate the expression of INSL-3 in human thyroid carcinoma cell lines and thyroid gland tissues.
- To determine if INSL-3 isoforms can serve as biomarkers for thyroid hyperplasias and carcinomas.
- To explore the potential hormonal regulation of INSL-3 and its receptor LGR8 in thyroid cancer.
Main Methods:
- Expression analysis of INSL-3 in eight human thyroid carcinoma cell lines.
- In situ hybridization to detect INSL-3 transcripts and immunohistochemistry using specific antisera for INSL-3 protein detection in patient tissues.
- Treatment of an anaplastic thyroid carcinoma cell line (8505C) with diethylstilbestrol (DES) to assess transcriptional regulation of INSL-3 and LGR8.
Main Results:
- A novel INSL-3 splice variant with a 95 bp out-of-frame insertion in exon II was discovered in thyroid carcinoma cell lines.
- Both INSL-3 isoforms were detected in Graves' disease, follicular, papillary, and anaplastic thyroid carcinomas, but not in benign goiter tissues.
- Diethylstilbestrol (DES) treatment significantly downregulated INSL-3 and upregulated LGR8 in the 8505C anaplastic thyroid carcinoma cell line.
Conclusions:
- INSL-3 hormone is upregulated in hyperplastic and neoplastic human thyrocytes, indicating its potential as an additional marker for these conditions.
- The findings suggest a novel, hormonally responsive auto-/paracrine INSL-3/LGR8 ligand-receptor system active in human thyroid carcinoma cells.
- INSL-3 isoforms may serve as valuable biomarkers for diagnosing and understanding thyroid hyperplastic and neoplastic diseases.