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Published on: November 17, 2018
Low-density lipoprotein receptor-related protein 1 is an essential receptor for trichosanthin in 2 choriocarcinoma
1Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Abstract:
Type-I ribosome-inactivating protein-trichosanthin (TCS) exhibits selective cytotoxicity toward different types of cells. It is believed that the cytotoxicity results from the inhibition of ribosomes to decrease protein synthesis, thereby indicating that there are specific mechanisms for TCS entry into target cells to reach the ribosomes. Low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a large scavenger receptor that is responsible for the binding and endocytosis of diverse biological ligands on the cell surface. In this study, we demonstrated that 2 choriocarcinoma cell lines can significantly bind and internalize TCS. In contrast, Hela cell line displayed no obvious TCS binding and endocytosis. Furthermore LRP1 gene silencing in JAR and BeWo cell lines blocked TCS binding; TCS could also interact with LRP1.The results of our study established that LRP1 was a major receptor for phagocytosis of TCS in JAR and BeWo cell lines and might be the molecular basis of TCS abortificient and anti-choriocarcinoma activity.
Insights
Type-I ribosome-inactivating protein (TCS) selectively targets cells. Researchers found Low-density lipoprotein receptor-related protein 1 (LRP1) acts as a key receptor for TCS entry into choriocarcinoma cells, explaining its activity.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Type-I ribosome-inactivating proteins, like trichosanthin (TCS), display selective cytotoxicity.
- TCS exerts its effects by inhibiting protein synthesis, necessitating specific cellular uptake mechanisms.
- Low-density lipoprotein receptor-related protein 1 (LRP1) is a scavenger receptor involved in endocytosis of various ligands.
Purpose of the Study:
- To investigate the cellular uptake mechanisms of trichosanthin (TCS).
- To identify the specific cell surface receptor responsible for TCS binding and internalization.
- To elucidate the role of LRP1 in TCS activity against choriocarcinoma cells.
Main Methods:
- Comparing TCS binding and internalization in choriocarcinoma cell lines (JAR, BeWo) and Hela cells.
- Utilizing LRP1 gene silencing in JAR and BeWo cells.
- Assessing the interaction between TCS and LRP1.
Main Results:
- Choriocarcinoma cell lines (JAR, BeWo) demonstrated significant binding and internalization of TCS.
- Hela cells showed minimal TCS binding and internalization.
- LRP1 gene silencing abrogated TCS binding in JAR and BeWo cells, indicating LRP1's crucial role.
- TCS was shown to interact directly with LRP1.
Conclusions:
- Low-density lipoprotein receptor-related protein 1 (LRP1) is identified as a major receptor for TCS uptake in choriocarcinoma cells.
- LRP1-mediated phagocytosis of TCS is likely the molecular basis for its abortifacient and anti-choriocarcinoma effects.
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