RETRACTED: Endogenous production of C–C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis

Autor: Lin Quan Tang, Xue Song Sun, Li Ting Liu, Ling Guo, Wen Wen Hao, Jin Xin Bei, Chao Nan Qian, Hai Qiang Mai, Yan Xian Li, Qing Nan Tang, Mu Sheng Zeng, Dan Ni Chen, Yang Li, Rui Liu, Qiu Yan Chen, Hao Yuan Mo, Jing Yun Peng, Shan Shan Guo, Li Yuan, Yue Feng Wen, Shu Yang Sun
Rok vydání: 2020
Předmět:
Adult
Male
0301 basic medicine
Cancer Research
Chemokine
Epithelial-Mesenchymal Transition
Organoplatinum Compounds
CCL2
Radiation Tolerance
Disease-Free Survival
Metastasis
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Radioresistance
otorhinolaryngologic diseases
medicine
Humans
Epithelial–mesenchymal transition
Progression-free survival
Autocrine signalling
Chemokine CCL2
Nasopharyngeal Carcinoma
biology
business.industry
Nasopharyngeal Neoplasms
Chemoradiotherapy
Middle Aged
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
Progression-Free Survival
Gene Expression Regulation
Neoplastic
Autocrine Communication
stomatognathic diseases
030104 developmental biology
Oncology
Nasopharyngeal carcinoma
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Cisplatin
Neoplasm Recurrence
Local
Tumor Suppressor Protein p53
business
Signal Transduction
Zdroj: Cancer Letters. 468:27-40
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2019.10.008
Popis: Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.
Databáze: OpenAIRE
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