Related Experiment Video
Updated: May 6, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis
Wen-guo Jiang1, Xin-an Lu, Bo-yang Shang
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P, R, China. yluo@tsinghua.edu.cn.
Background:
Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety.
Methods:
In this study, we designed and obtained two new endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the wound healing assay and tube formation assay and the cytotoxicity of their enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was evaluated with human lung carcinoma PG-BE1 xenograft and the experimental metastasis model of 4T1-luc breast cancer.
Results:
ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice.
Conclusions:
The ES-based fusion protein therapy provides some fundamental information for further drug development. Targeting both tumor vasculature and tumor cells by endostatin-based fusion proteins and their enediyne-energized analogs probably provides a promising modality in cancer therapy.
Insights
This study developed novel endostatin-lidamycin (ES-LDM) fusion proteins that target tumor vasculature and cancer cells. The fusion proteins demonstrated significant anti-tumor efficacy in preclinical models, offering a promising new cancer therapy approach.
Area of Science:
- Biotechnology
- Cancer Research
- Drug Development
Background:
- Endostatin (ES) inhibits angiogenesis and tumor growth by targeting tumor vasculature.
- Lidamycin (LDM) is a potent antitumor antibiotic targeting cancer cells.
- Fusion proteins combine ES and LDM functionalities for dual targeting.
Purpose of the Study:
- To design and evaluate novel endostatin-based fusion proteins (ES-LDP and LDP-ES).
- To assess the antiangiogenic and cytotoxic effects of these fusion proteins and their enediyne-energized analogs.
- To investigate their in vivo efficacy in preclinical cancer models.
Main Methods:
- Designed and synthesized endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES) fusion proteins.
- Evaluated in vitro antiangiogenic effects using wound healing and tube formation assays.
- Assessed cytotoxicity and binding affinity using CCK-8 assay and tissue microarrays.
- Determined in vivo efficacy in human lung carcinoma and breast cancer metastasis models.
Main Results:
- ES-LDP and LDP-ES inhibited endothelial cell migration and tube formation.
- ES-LDP demonstrated tumor accumulation, suppressed tumor growth, and reduced metastasis.
- ES-LDP and ES showed superior binding to lung carcinoma compared to LDP.
- Enediyne-energized ES-LDP-AE exhibited significant efficacy against lung carcinoma xenografts.
Conclusions:
- Endostatin-based fusion proteins offer a dual-targeting strategy for cancer therapy.
- These fusion proteins and their analogs provide fundamental insights for future drug development.
- Targeting both tumor vasculature and tumor cells represents a promising cancer treatment modality.
More Related Videos
12:14CAM-Delam Assay to Score Metastatic Properties by Quantifying Delamination and Invasion Capacity of Cancer Cells
Published on: June 2, 2022
10:32Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
Published on: December 19, 2019
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:27Tumor Immunotherapy
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...