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Conference Paper: CCL2/CCR2 axis signaling promotes metastasis of nasopharyngeal carcinoma by activating ERK1/2 pathway via upregulating MMP2 and MMP9

TitleCCL2/CCR2 axis signaling promotes metastasis of nasopharyngeal carcinoma by activating ERK1/2 pathway via upregulating MMP2 and MMP9
Authors
Issue Date2015
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Proceedings of the 106th Annual Meeting of the American Association for Cancer Research (AACR 2015), Philadelphia, PA., 18-22 April 2015. In Cancer Research, 2015, v. 75 n. 15, Suppl., p. Abstract no. 2254 How to Cite?
AbstractDespite tremendous progress in diagnosis and treatments of nasopharyngeal carcinoma (NPC) has been established nowadays, distant metastasis remains the major cause of death.The underlying molecular mechanisms are largely unknown. In the present study,we investigated the roles in NPCs for an axis of candidate metastasis-related genes located at 17q11.2-q12, chemokine C-C motif ligand 2 (CCL2), and located at 3p21.31, chemokine C-C motif receptor 2 (CCR2). ELISA analyses of human serum from 50 cases with NPC and 50 cases without NPC revealed the mean serum CCL2 concentration of cases with NPC was significantly higher than cases without NPC (P<0.001).Higher expression levels of CCL2 and CCR2 were frequently detected in NPCs compared with normal nasopharyngeal epithelium samples by IHC analyses, and both ectopic expressions were significantly associated with NPC metastasis (P = 0.039, p = 0.016, respectively) and poor overall survival (P = 0.011, p = 0.004, respectively). Overexpressions of CCL2 and CCR2 were observed in human strong-metastatic NPC cell line S18 originated from CNE2 and 58F originated from SUNE1. Correspondingly, relatively lower expressions of CCL2 and CCR2 were detected in human weak-metastatic NPC cell line S26 originated from CNE2 and SUNE1 with weaker-metastatic ability compared to 58F. Functional studies demonstrated that upregulating the expressions of CCL2 and CCR2 respectively in S26 and SUNE1 could effectively promote cell migration and invasion in vitro, and enhance tumor distant metastasis in vivo of nude mice, which could be further raised in cells overexpressing CCR2 with exogenous CCL2 in the medium. When CCL2 and CCR2 were silenced by shRNAs respectively in S18 and 58F, decrease of cell migration and invasion was showed and significantly fewer metastases were observed. However, adding exogenous CCL2 to the medium culturing CCR2-silencing cells could not rescue their weaken ability of migration and invasion and metastasis. Mechanistic investigations suggested that, dual overexpressions of CCL2/CCR2 could remarkably activate extracellular signal-regulated kinase (ERK1/2) signaling pathway, which sequentially induced matrix metalloproteinase (MMP)2/9 transcriptional activation to facilitate tumor metastasis. Taken as a whole, CCL2-CCR2 axis signaling plays a pivotal role in NPC metastasis by activating ERK1/2 pathway via upregulating MMP2 and MMP9, and this finding may help to identify novel therapeutic targets for a better clinical management of NPC.
Persistent Identifierhttp://hdl.handle.net/10722/244465
ISSN
2017 Impact Factor: 9.13
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorYang, J-
dc.contributor.authorLv, X-
dc.contributor.authorXiang, Y-
dc.contributor.authorGuo, X-
dc.contributor.authorChen, J-
dc.contributor.authorGuan, X-
dc.date.accessioned2017-09-18T01:52:58Z-
dc.date.available2017-09-18T01:52:58Z-
dc.date.issued2015-
dc.identifier.citationProceedings of the 106th Annual Meeting of the American Association for Cancer Research (AACR 2015), Philadelphia, PA., 18-22 April 2015. In Cancer Research, 2015, v. 75 n. 15, Suppl., p. Abstract no. 2254-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/244465-
dc.description.abstractDespite tremendous progress in diagnosis and treatments of nasopharyngeal carcinoma (NPC) has been established nowadays, distant metastasis remains the major cause of death.The underlying molecular mechanisms are largely unknown. In the present study,we investigated the roles in NPCs for an axis of candidate metastasis-related genes located at 17q11.2-q12, chemokine C-C motif ligand 2 (CCL2), and located at 3p21.31, chemokine C-C motif receptor 2 (CCR2). ELISA analyses of human serum from 50 cases with NPC and 50 cases without NPC revealed the mean serum CCL2 concentration of cases with NPC was significantly higher than cases without NPC (P<0.001).Higher expression levels of CCL2 and CCR2 were frequently detected in NPCs compared with normal nasopharyngeal epithelium samples by IHC analyses, and both ectopic expressions were significantly associated with NPC metastasis (P = 0.039, p = 0.016, respectively) and poor overall survival (P = 0.011, p = 0.004, respectively). Overexpressions of CCL2 and CCR2 were observed in human strong-metastatic NPC cell line S18 originated from CNE2 and 58F originated from SUNE1. Correspondingly, relatively lower expressions of CCL2 and CCR2 were detected in human weak-metastatic NPC cell line S26 originated from CNE2 and SUNE1 with weaker-metastatic ability compared to 58F. Functional studies demonstrated that upregulating the expressions of CCL2 and CCR2 respectively in S26 and SUNE1 could effectively promote cell migration and invasion in vitro, and enhance tumor distant metastasis in vivo of nude mice, which could be further raised in cells overexpressing CCR2 with exogenous CCL2 in the medium. When CCL2 and CCR2 were silenced by shRNAs respectively in S18 and 58F, decrease of cell migration and invasion was showed and significantly fewer metastases were observed. However, adding exogenous CCL2 to the medium culturing CCR2-silencing cells could not rescue their weaken ability of migration and invasion and metastasis. Mechanistic investigations suggested that, dual overexpressions of CCL2/CCR2 could remarkably activate extracellular signal-regulated kinase (ERK1/2) signaling pathway, which sequentially induced matrix metalloproteinase (MMP)2/9 transcriptional activation to facilitate tumor metastasis. Taken as a whole, CCL2-CCR2 axis signaling plays a pivotal role in NPC metastasis by activating ERK1/2 pathway via upregulating MMP2 and MMP9, and this finding may help to identify novel therapeutic targets for a better clinical management of NPC.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleCCL2/CCR2 axis signaling promotes metastasis of nasopharyngeal carcinoma by activating ERK1/2 pathway via upregulating MMP2 and MMP9-
dc.typeConference_Paper-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.doi10.1158/1538-7445.AM2015-2254 -
dc.identifier.hkuros276972-
dc.identifier.volume75-
dc.identifier.issue15, Suppl.-
dc.identifier.spageAbstract no. 2254-
dc.identifier.epageAbstract no. 2254-
dc.publisher.placeUnited States-

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