Related Experiment Video
Updated: Dec 26, 2025
Circulating Tumor Cell Lines: an Innovative Tool for Fundamental and Translational Research
Published on: December 25, 2021
Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models
Ludmila A Alekseeva1, Aleksandra V Sen'kova1, Marina A Zenkova1
1Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, Russia.
Abstract:
Tumor-associated cell-free DNAs (cfDNAs) are found to play some important roles at different stages of tumor progression; they are involved in the transformation of normal cells and contribute to tumor migration and invasion. DNase I is considered a promising cancer cure, due to its ability to degrade cfDNAs. Previous studies using murine tumor models have proved the high anti-metastatic potential of DNase I. Later circulating cfDNAs, especially tandem repeats associated with short-interspersed nuclear elements (SINEs) and long-interspersed nuclear elements (LINEs), have been found to be the enzyme's main molecular targets. Here, using Lewis lung carcinoma, melanoma B16, and lymphosarcoma RLS40 murine tumor models, we reveal that tumor progression is accompanied by an increase in the level of SINE and LINEs in the pool of circulating cfDNAs. Treatment with DNase I decreased in the number and area of metastases by factor 3-10, and the size of the primary tumor node by factor 1.5-2, which correlated with 5- to 10-fold decreasing SINEs and LINEs. We demonstrated that SINEs and LINEs from cfDNA of tumor-bearing mice are able to penetrate human cells. The results show that SINEs and LINEs could be important players in metastasis, and this allows them to be considered as attractive new targets for anticancer therapy.
Insights
Tumor-associated cell-free DNAs (cfDNAs), particularly short-interspersed nuclear elements (SINEs) and long-interspersed nuclear elements (LINEs), drive cancer metastasis. DNase I treatment effectively reduces tumor growth and metastasis by degrading these cfDNAs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor-associated cell-free DNAs (cfDNAs) influence cancer progression, including cell transformation, migration, and invasion.
- DNase I, an enzyme that degrades cfDNAs, shows potential as an anti-cancer therapeutic.
- Previous research indicated DNase I's anti-metastatic properties in murine models, targeting circulating cfDNAs like SINEs and LINEs.
Purpose of the Study:
- To investigate the role of short-interspersed nuclear elements (SINEs) and long-interspersed nuclear elements (LINEs) in cfDNA during tumor progression.
- To evaluate the efficacy of DNase I in reducing tumor growth and metastasis in established murine cancer models.
- To determine if SINEs and LINEs from tumor-bearing mice can impact human cells.
Main Methods:
- Utilized Lewis lung carcinoma, melanoma B16, and lymphosarcoma RLS40 murine tumor models.
- Quantified cfDNA levels, specifically SINEs and LINEs, during tumor progression.
- Administered DNase I treatment and assessed its impact on metastasis and primary tumor size.
- Investigated the cellular uptake of cfDNA SINEs and LINEs in human cells.
Main Results:
- Tumor progression correlated with increased levels of SINEs and LINEs in circulating cfDNA.
- DNase I treatment reduced metastasis by 3-10 fold and primary tumor size by 1.5-2 fold.
- The reduction in tumor burden by DNase I corresponded with a 5- to 10-fold decrease in SINEs and LINEs.
- SINEs and LINEs from cfDNA of tumor-bearing mice were observed to penetrate human cells.
Conclusions:
- SINEs and LINEs in cfDNA are significantly elevated during tumor progression and play a role in metastasis.
- DNase I effectively combats tumor growth and metastasis by targeting these cfDNA elements.
- SINEs and LINEs represent promising novel therapeutic targets for anticancer strategies.
