Radiotherapy-induced cell death activates paracrine HMGB1-TLR2 signaling and accelerates pancreatic carcinoma metastasis

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Xuelian Chen, Lirong Zhang, Yujie Jiang, Lian Song, Yanfang Liu, Fang Cheng, Xin Fan, Xiongfeng Cao, Aihua Gong, Dongqing Wang, Haitao Zhu
Förläggare: BMC
Publiceringsår: 2018
Tidskrift: Journal of Experimental and Clinical Cancer Research
Tidskriftsakronym: J EXP CLIN CANC RES
Volym: 37
Antal sidor: 15
ISSN: 1756-9966


Abstrakt

Background: Dying cells after irradiation could promote the repopulation of surviving cancer cells leading to tumor recurrence. We aim to define the role of dying cells in promoting pancreatic cancer cells metastasis following radiotherapy.Methods: Using the transwell system as the in vitro co-culture model, a small number of untreated pancreatic cancer cells were seeded in the upper chamber, while a larger number of lethally treated pancreatic cancer cells were seeded in the lower chamber. A series of experiments were conducted to investigate the role of dying-cell-derived HMGB1 on the invasion of pancreatic cancer in vitro and cancer metastasis in vivo. We then designed shRNA knockdown and Western blot assays to detect signaling activity.Results: We found that dying pancreatic cancer cells significantly promote the invasion of pancreatic cancer cells in vitro and cancer metastasis in vivo. HMGB1 gene knockdown attenuated the migration-stimulating effect of irradiated, dying cells on living pancreatic cancer cells. Finally, we showed that dying-cell-derived HMGB1 functions in a paracrine manner to affect cancer-cell migration dependent on acquiring an epithelial-mesenchymal transition (EMT) phenotype and PI3K/pAkt activation. This process is mediated by the receptor for TLR2.Conclusion: Our study indicates that, during radiotherapy, dying pancreatic cancer cells activate paracrine signaling events that promote the mobility of surviving tumor cells. We suggest a strategy to inhibit HMGB1 for preventing pancreatic carcinoma relapse and metastasis.


Nyckelord

HMGB1, metastasis, Pancreatic carcinoma, Radiotherapy

Senast uppdaterad 2019-21-11 vid 04:06