Jagged1 contained in MSC-derived small extracellular vesicles promotes squamous differentiation of cervical cancer by activating NOTCH pathway

Weizhao Li & Tian Li et al. · 2023-11-23

Abstract

Purpose

Cervical cancer is the fourth most common cancer in women and poses a major threat to women's health, urgently requiring new treatment methods.

Methods

This study first successfully extracted and identified small extracellular vesicles secreted by human umbilical cord-derived mesenchymal stem cells. We studied the effects of MSC-sEV on the squamous differentiation levels of cervical cancer CaSki cells in vitro, and explored the effects of MSC-sEV on the NOTCH pathway, the growth, proliferation, migration abilities and squamous differentiation levels of cervical cancer cells. The roles of MSC-sEV were also verified in human keratinocyte HaCaT cells.

Results

The results showed that Jagged1 protein on MSC-sEV can bind to NOTCH1 on cervical cancer cells, activate NOTCH signaling, and promote squamous differentiation levels in CaSki cells, thus inhibiting the growth, proliferation and migration abilities of CaSki cells. MSC-sEV can also activate the NOTCH pathway in HaCaT cells, but promote the viability of HaCaT cells.

Conclusion

MSC-sEV can activate the NOTCH pathway to promote squamous differentiation of CaSki cells and inhibit the growth proliferation and migration abilities of CaSki cells which may be a new mechanism for cervical cancer treatment.

Authors
Weizhao Li, Xunzhi Zhang, Tianshun Gao, Lixiang Liu, Chi Zhang, Huan Yang, Jiayuan Xie, Wei Pan, David Y. B. Deng, Changlin Zhang, Tian Li
Funding

National Natural Science Foundation of China

82002899

National Natural Science Foundation of China

82172883

Natural Science Foundation of Guangdong Province

2023A1515012662

Natural Science Foundation of Guangdong Province

2022A1515012444