OC 38.5 - Platelets promote hepatocellular carcinoma metastasis through releasing TGF-β1-mediated cancer cell autophagy

Monday, June 24, 2024

10:30 – 10:45 ICT

Room: 211 A-D

Presenting Author(s)

Zhangyin Ming, MD,PhD

professor
Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
Wuhan, Hubei, China (People's Republic)

Co-Author(s)

ML

Meng Lu

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
XG

Xue Gong

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
Yumin Zhang, MA

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
YG

Yawei Guo

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
XZ

Xiangbin Zeng

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
JG

Jiahui Gao

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)
QL

Qi Luo

student
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
Wuhan, Hubei, China (People's Republic)

Background: Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs) once they enter the bloodstream.

Aims: To explore the role of platelets in the epithelial mesenchymal transition (EMT) of cancer cells within the primary tumor.

Methods: Cell culture, migration and invasion assay were used to check the activated platelet releasate effect on HCC in vitro. Orthotopic cancer metastasis model was used to check the tumor microenvironment TGF-β1 content, autophagy, and lung metastasis in platelet specific deletion of TGF-β1 mice. Additionally, pharmacologic inhibitor of autophagy or autophagy gene silencing was used to explore the role of autophagy in these processes.

Results: In this study, we found that platelet releasate significantly increased HCC cells EMT and motility in vitro. In mechanism, this was mediated by TGF-β1-induced HCC cell autophagy via the AMPK/mTOR pathway. In vivo, specific deletion of TGF-β1 in platelets decreased TGF-β1 content within the primary tumor, and subsequently inhibited cancer cell EMT, autophagy, migration and tumor metastasis. Autophagy inhibition through Atg5 knockdown effectively counteracted the EMT of cancer cells within the primary tumor and HCC metastasis induced by platelet-released TGF-β1. Notably, in HCC patients, higher platelet count was correlated with increased TGF-β1 content, elevated CDH2 and LC3 expression within the primary tumor. It also showed positive correlation among TGF-β1 content, CDH2 and LC3 expression within the primary tumor.

Conclusion(s): Platelets promoted cancer cell EMT within primary tumor and, consequently, HCC metastasis through their releasate. This was mediated by TGF-β1-induced HCC cell autophagy via the AMPK/mTOR pathway.