In silico experimentation of glioma microenvironment development and anti-tumor therapy.

Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemi...

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Autores principales:	Yu Wu, Yao Lu, Weiqiang Chen, Jianping Fu, Rong Fan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6fbc65b57a2a4a96994dc4b67ec1afc4
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spelling	oai:doaj.org-article:6fbc65b57a2a4a96994dc4b67ec1afc42021-11-18T05:51:37ZIn silico experimentation of glioma microenvironment development and anti-tumor therapy.1553-734X1553-735810.1371/journal.pcbi.1002355https://doaj.org/article/6fbc65b57a2a4a96994dc4b67ec1afc42012-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22319429/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but strikingly no therapeutic efficacy at all when therapy was given at a slightly later stage. Cytokine combination therapy exhibits more focused and enhanced therapeutic response even when microglia depletion therapy already fails. It was further revealed that the optimal combination depends on the molecular profile of individual patients, suggesting the need for patient stratification and personalized treatment. These results, obtained solely by observing the in silico dynamics of the glioma microenvironment with no fitting to experimental/clinical data, reflect many characteristics of human glioma development and imply new venues for treating tumors via selective targeting of microenvironmental components.Yu WuYao LuWeiqiang ChenJianping FuRong FanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 2, p e1002355 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yu Wu Yao Lu Weiqiang Chen Jianping Fu Rong Fan In silico experimentation of glioma microenvironment development and anti-tumor therapy.
description	Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but strikingly no therapeutic efficacy at all when therapy was given at a slightly later stage. Cytokine combination therapy exhibits more focused and enhanced therapeutic response even when microglia depletion therapy already fails. It was further revealed that the optimal combination depends on the molecular profile of individual patients, suggesting the need for patient stratification and personalized treatment. These results, obtained solely by observing the in silico dynamics of the glioma microenvironment with no fitting to experimental/clinical data, reflect many characteristics of human glioma development and imply new venues for treating tumors via selective targeting of microenvironmental components.
format	article
author	Yu Wu Yao Lu Weiqiang Chen Jianping Fu Rong Fan
author_facet	Yu Wu Yao Lu Weiqiang Chen Jianping Fu Rong Fan
author_sort	Yu Wu
title	In silico experimentation of glioma microenvironment development and anti-tumor therapy.
title_short	In silico experimentation of glioma microenvironment development and anti-tumor therapy.
title_full	In silico experimentation of glioma microenvironment development and anti-tumor therapy.
title_fullStr	In silico experimentation of glioma microenvironment development and anti-tumor therapy.
title_full_unstemmed	In silico experimentation of glioma microenvironment development and anti-tumor therapy.
title_sort	in silico experimentation of glioma microenvironment development and anti-tumor therapy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6fbc65b57a2a4a96994dc4b67ec1afc4
work_keys_str_mv	AT yuwu insilicoexperimentationofgliomamicroenvironmentdevelopmentandantitumortherapy AT yaolu insilicoexperimentationofgliomamicroenvironmentdevelopmentandantitumortherapy AT weiqiangchen insilicoexperimentationofgliomamicroenvironmentdevelopmentandantitumortherapy AT jianpingfu insilicoexperimentationofgliomamicroenvironmentdevelopmentandantitumortherapy AT rongfan insilicoexperimentationofgliomamicroenvironmentdevelopmentandantitumortherapy
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In silico experimentation of glioma microenvironment development and anti-tumor therapy.

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