Cargando…

Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC

Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Yu, Li, Shan, Ma, Liping, Li, Yan, Zhang, Xiaolian, Peng, Qiliu, Mo, Cuiju, Huang, Li, Qin, Xue, Liu, Yinkun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846822/
https://www.ncbi.nlm.nih.gov/pubmed/27117207
http://dx.doi.org/10.1038/srep24558
_version_ 1782429110014836736
author Lu, Yu
Li, Shan
Ma, Liping
Li, Yan
Zhang, Xiaolian
Peng, Qiliu
Mo, Cuiju
Huang, Li
Qin, Xue
Liu, Yinkun
author_facet Lu, Yu
Li, Shan
Ma, Liping
Li, Yan
Zhang, Xiaolian
Peng, Qiliu
Mo, Cuiju
Huang, Li
Qin, Xue
Liu, Yinkun
author_sort Lu, Yu
collection PubMed
description Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration, and invasion abilities of SMMC7721 cells (all P < 0.05). M2 were then co-cultured with SMMC7721 cells to reconstruct the tumor microenvironment. Conditioned medium from 3D single cultures of M2, SMMC7721 cells, and their co-culture system were analyzed using quantitative proteomics via iTRAQ labeling combined with mass spectrometric analysis. Secretome analysis revealed a total of 159 differential secreted proteins in the co-culture system compared to the single culture systems, with 63 being up-regulated (>1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues, and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells, and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis.
format Online
Article
Text
id pubmed-4846822
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-48468222016-04-29 Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC Lu, Yu Li, Shan Ma, Liping Li, Yan Zhang, Xiaolian Peng, Qiliu Mo, Cuiju Huang, Li Qin, Xue Liu, Yinkun Sci Rep Article Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration, and invasion abilities of SMMC7721 cells (all P < 0.05). M2 were then co-cultured with SMMC7721 cells to reconstruct the tumor microenvironment. Conditioned medium from 3D single cultures of M2, SMMC7721 cells, and their co-culture system were analyzed using quantitative proteomics via iTRAQ labeling combined with mass spectrometric analysis. Secretome analysis revealed a total of 159 differential secreted proteins in the co-culture system compared to the single culture systems, with 63 being up-regulated (>1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues, and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells, and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis. Nature Publishing Group 2016-04-27 /pmc/articles/PMC4846822/ /pubmed/27117207 http://dx.doi.org/10.1038/srep24558 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lu, Yu
Li, Shan
Ma, Liping
Li, Yan
Zhang, Xiaolian
Peng, Qiliu
Mo, Cuiju
Huang, Li
Qin, Xue
Liu, Yinkun
Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title_full Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title_fullStr Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title_full_unstemmed Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title_short Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
title_sort type conversion of secretomes in a 3d tam2 and hcc cell co-culture system and functional importance of cxcl2 in hcc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846822/
https://www.ncbi.nlm.nih.gov/pubmed/27117207
http://dx.doi.org/10.1038/srep24558
work_keys_str_mv AT luyu typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT lishan typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT maliping typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT liyan typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT zhangxiaolian typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT pengqiliu typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT mocuiju typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT huangli typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT qinxue typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc
AT liuyinkun typeconversionofsecretomesina3dtam2andhcccellcoculturesystemandfunctionalimportanceofcxcl2inhcc