Related Experiment Video
Updated: Jul 4, 2026
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic
Susanna Vuorenoja1, Adolfo Rivero-Müller, Adam J Ziecik
1Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Abstract:
Novel strategies are needed for the treatment of adrenocortical tumors that are usually resistant to chemotherapy. Hecate, a 23-amino acid lytic peptide, was conjugated to the 15-amino acid (81-95) fragment of the human chorionic gonadotropin beta (CGbeta) chain, which would selectively kill cancer cells expressing the LH receptor (LHR) sparing the normal ones with LHR. To prove the principle that Hecate-CGbeta conjugate may eradicate tumors ectopically expressing plasma membrane receptors, transgenic (TG) inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen mice, expressing LHR in their adrenal gland tumors, were used as the experimental model. Wild-type control littermates and TG mice with adrenal tumors were treated with either Hecate or Hecate-CGbeta conjugate at the age of 6.5 months for 3 weeks and killed 7 days after the last treatment. The Hecate-CGbeta conjugate reduced the adrenal tumor burden significantly in TG male but not in female mice, in comparison with Hecate-treated mice. Hecate-CGbeta conjugate treatment did not affect normal adrenocortical function as the serum corticosterone level between Hecate and Hecate-CGbeta conjugate groups were similar. The mRNA and protein expressions of GATA-4 and LHR colocalized only in tumor area, and a significant downregulation of gene expression was found after the Hecate-CGbeta conjugate in comparison with Hecate- and/or non-treated adrenal tumors by western blotting. This finding provides evidence for a selective destruction of the tumor cells by the Hecate-CGbeta conjugate. Hereby, our findings support the principle that Hecate-CGbeta conjugate is able to specifically destroy tumor cells that ectopically express LHR.
Insights
A novel Hecate-CGbeta conjugate effectively targets and reduces adrenal tumors by selectively destroying cancer cells expressing the LH receptor (LHR). This targeted approach spares normal cells, offering a promising new strategy for treating chemotherapy-resistant adrenocortical tumors.
Area of Science:
- Oncology
- Endocrinology
- Biotechnology
Background:
- Adrenocortical tumors often resist conventional chemotherapy.
- Targeted therapies are needed to selectively eliminate cancer cells while preserving normal tissue function.
Purpose of the Study:
- To evaluate the efficacy of a novel Hecate-CGbeta conjugate in treating adrenocortical tumors.
- To determine if the conjugate selectively targets cancer cells expressing the luteinizing hormone receptor (LHR).
Main Methods:
- A Hecate-CGbeta conjugate was developed by linking a lytic peptide (Hecate) to a human chorionic gonadotropin beta (CGbeta) fragment.
- Transgenic mice with adrenal tumors expressing LHR were treated with Hecate or Hecate-CGbeta conjugate.
- Tumor burden, gene expression (GATA-4, LHR), and serum corticosterone levels were analyzed.
Main Results:
- Hecate-CGbeta conjugate significantly reduced adrenal tumor burden in male transgenic mice compared to Hecate alone.
- No significant difference in serum corticosterone levels was observed between treatment groups, indicating preserved normal adrenocortical function.
- Downregulation of GATA-4 and LHR gene expression was observed in tumors treated with the conjugate.
Conclusions:
- The Hecate-CGbeta conjugate demonstrates selective destruction of adrenocortical tumor cells expressing LHR.
- This conjugate represents a potential targeted therapeutic strategy for LHR-expressing adrenocortical tumors.
More Related Videos
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
10:47Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
