Abstract:
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.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Chen X,Zhang L,Jiang Y,Song L,Liu Y,Cheng F,Fan X,Cao X,Gong A,Wang D,Zhu Hdoi
10.1186/s13046-018-0726-2subject
Has Abstractpub_date
2018-04-03 00:00:00pages
77issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-018-0726-2journal_volume
37pub_type
杂志文章abstract:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with dismal prognosis and high incidence and mortality in Kazakh population. MiR-34a, a direct p53 target gene, possesses tumor-suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. The reduced expression of miR-3...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-33-20
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journal_title:Journal of experimental & clinical cancer research : CR
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abstract::In the original publication of this article [1], the authors reported the order of the authors was incorrect and needs to be revised. The original article has been updated to rectify this error. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
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abstract:BACKGROUND:MicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates th...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1079-1
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
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doi:
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-09-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,撤回出版物
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