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

Shan Shan Guo, Rui Liu, Yue Feng Wen, Li Ting Liu, Li Yuan, Yan Xian Li, Yang Li, Wen Wen Hao, Jing Yun Peng, Dan Ni Chen, Qing Nan Tang, Xue Song Sun, Ling Guo, Hao Yuan Mo, Chao Nan Qian, Mu Sheng Zeng, Jin Xin Bei, Shu Yang Sun, Qiu Yan Chen, Lin Quan TangHai Qiang Mai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalCancer Letters
Volume468
DOIs
StatePublished - Jan 1 2020

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CC Chemokines
Neoplasm Metastasis
Ligands
Autocrine Communication
Recurrence
Epithelial-Mesenchymal Transition
Survival
Nasopharyngeal carcinoma
Disease-Free Survival
Radiotherapy

Keywords

  • C–C motif chemokine ligand 2
  • Epithelial-mesenchymal transition
  • Metastasis
  • Nasopharyngeal carcinoma
  • Radioresistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Endogenous production of C–C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis. / Guo, Shan Shan; Liu, Rui; Wen, Yue Feng; Liu, Li Ting; Yuan, Li; Li, Yan Xian; Li, Yang; Hao, Wen Wen; Peng, Jing Yun; Chen, Dan Ni; Tang, Qing Nan; Sun, Xue Song; Guo, Ling; Mo, Hao Yuan; Qian, Chao Nan; Zeng, Mu Sheng; Bei, Jin Xin; Sun, Shu Yang; Chen, Qiu Yan; Tang, Lin Quan; Mai, Hai Qiang.

In: Cancer Letters, Vol. 468, 01.01.2020, p. 27-40.

Research output: Contribution to journalArticle

Guo, SS, Liu, R, Wen, YF, Liu, LT, Yuan, L, Li, YX, Li, Y, Hao, WW, Peng, JY, Chen, DN, Tang, QN, Sun, XS, Guo, L, Mo, HY, Qian, CN, Zeng, MS, Bei, JX, Sun, SY, Chen, QY, Tang, LQ & Mai, HQ 2020, 'Endogenous production of C–C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis', Cancer Letters, vol. 468, pp. 27-40. https://doi.org/10.1016/j.canlet.2019.10.008
Guo, Shan Shan ; Liu, Rui ; Wen, Yue Feng ; Liu, Li Ting ; Yuan, Li ; Li, Yan Xian ; Li, Yang ; Hao, Wen Wen ; Peng, Jing Yun ; Chen, Dan Ni ; Tang, Qing Nan ; Sun, Xue Song ; Guo, Ling ; Mo, Hao Yuan ; Qian, Chao Nan ; Zeng, Mu Sheng ; Bei, Jin Xin ; Sun, Shu Yang ; Chen, Qiu Yan ; Tang, Lin Quan ; Mai, Hai Qiang. / Endogenous production of C–C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis. In: Cancer Letters. 2020 ; Vol. 468. pp. 27-40.
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abstract = "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.",
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AU - Guo, Shan Shan

AU - Liu, Rui

AU - Wen, Yue Feng

AU - Liu, Li Ting

AU - Yuan, Li

AU - Li, Yan Xian

AU - Li, Yang

AU - Hao, Wen Wen

AU - Peng, Jing Yun

AU - Chen, Dan Ni

AU - Tang, Qing Nan

AU - Sun, Xue Song

AU - Guo, Ling

AU - Mo, Hao Yuan

AU - Qian, Chao Nan

AU - Zeng, Mu Sheng

AU - Bei, Jin Xin

AU - Sun, Shu Yang

AU - Chen, Qiu Yan

AU - Tang, Lin Quan

AU - Mai, Hai Qiang

PY - 2020/1/1

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N2 - 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.

AB - 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.

KW - C–C motif chemokine ligand 2

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