Systems-level modeling of cancer-fibroblast interaction.
Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin de...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2731225?pdf=render |
| _version_ | 1819231497693954048 |
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| author | Raymond C Wadlow Ben S Wittner S Aidan Finley Henry Bergquist Rabi Upadhyay Stephen Finn Massimo Loda Umar Mahmood Sridhar Ramaswamy |
| author_facet | Raymond C Wadlow Ben S Wittner S Aidan Finley Henry Bergquist Rabi Upadhyay Stephen Finn Massimo Loda Umar Mahmood Sridhar Ramaswamy |
| author_sort | Raymond C Wadlow |
| collection | DOAJ |
| description | Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts. |
| first_indexed | 2024-12-23T11:45:54Z |
| format | Article |
| id | doaj.art-1d7e01f1bf294bd48c986682c0d204a1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T11:45:54Z |
| publishDate | 2009-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1d7e01f1bf294bd48c986682c0d204a12022-12-21T17:48:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e688810.1371/journal.pone.0006888Systems-level modeling of cancer-fibroblast interaction.Raymond C WadlowBen S WittnerS Aidan FinleyHenry BergquistRabi UpadhyayStephen FinnMassimo LodaUmar MahmoodSridhar RamaswamyCancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts.http://europepmc.org/articles/PMC2731225?pdf=render |
| spellingShingle | Raymond C Wadlow Ben S Wittner S Aidan Finley Henry Bergquist Rabi Upadhyay Stephen Finn Massimo Loda Umar Mahmood Sridhar Ramaswamy Systems-level modeling of cancer-fibroblast interaction. PLoS ONE |
| title | Systems-level modeling of cancer-fibroblast interaction. |
| title_full | Systems-level modeling of cancer-fibroblast interaction. |
| title_fullStr | Systems-level modeling of cancer-fibroblast interaction. |
| title_full_unstemmed | Systems-level modeling of cancer-fibroblast interaction. |
| title_short | Systems-level modeling of cancer-fibroblast interaction. |
| title_sort | systems level modeling of cancer fibroblast interaction |
| url | http://europepmc.org/articles/PMC2731225?pdf=render |
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