Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes
Systematic study of cell signaling networks increasingly involves high throughput proteomics, transcriptional profiling, and automated literature mining with the aim of assembling large-scale interaction networks. In contrast, functional analysis of cell signaling usually focuses on a much smaller s...
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Society for Biochemistry and Molecular Biology (ASBMB)
2013
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| Online Access: | http://hdl.handle.net/1721.1/76231 |
| _version_ | 1826203429000708096 |
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| author | Alexopoulos, Leonidas G. Rodriguez, Julio Saez Cosgrove, Benjamin D. Lauffenburger, Douglas A. Sorger, Peter K. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Alexopoulos, Leonidas G. Rodriguez, Julio Saez Cosgrove, Benjamin D. Lauffenburger, Douglas A. Sorger, Peter K. |
| author_sort | Alexopoulos, Leonidas G. |
| collection | MIT |
| description | Systematic study of cell signaling networks increasingly involves high throughput proteomics, transcriptional profiling, and automated literature mining with the aim of assembling large-scale interaction networks. In contrast, functional analysis of cell signaling usually focuses on a much smaller sets of proteins and eschews computation but focuses directly on cellular responses to environment and perturbation. We sought to combine these two traditions by collecting cellresponse measures on a reasonably large scale and then attempting to infer differences in network topology between two cell types. Human hepatocytes and hepatocellular carcinoma (HCC) cell lines were exposed to inducers of inflammation, innate immunity and proliferation in the presence and absence of small molecule drugs and multiplex biochemical measurement then performed on intra- and extracellular signaling molecules. We uncover major differences between primary and transformed hepatocytes with respect to the engagement of toll-like receptor and NF-κBdependent secretion of chemokines and cytokines that prime and attract immune cells. Overall, our results serve as a proof-of-principle for an approach to network analysis that is systematic, comparative and biochemically focused. More specifically, our data support the hypothesis that HCC cells down-regulate normal inflammatory and immune responses to avoid immune editing. |
| first_indexed | 2024-09-23T12:37:10Z |
| format | Article |
| id | mit-1721.1/76231 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:37:10Z |
| publishDate | 2013 |
| publisher | American Society for Biochemistry and Molecular Biology (ASBMB) |
| record_format | dspace |
| spelling | mit-1721.1/762312022-09-28T08:59:33Z Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes Alexopoulos, Leonidas G. Rodriguez, Julio Saez Cosgrove, Benjamin D. Lauffenburger, Douglas A. Sorger, Peter K. Massachusetts Institute of Technology. Department of Biological Engineering Cosgrove, Benjamin D. Lauffenburger, Douglas A. Systematic study of cell signaling networks increasingly involves high throughput proteomics, transcriptional profiling, and automated literature mining with the aim of assembling large-scale interaction networks. In contrast, functional analysis of cell signaling usually focuses on a much smaller sets of proteins and eschews computation but focuses directly on cellular responses to environment and perturbation. We sought to combine these two traditions by collecting cellresponse measures on a reasonably large scale and then attempting to infer differences in network topology between two cell types. Human hepatocytes and hepatocellular carcinoma (HCC) cell lines were exposed to inducers of inflammation, innate immunity and proliferation in the presence and absence of small molecule drugs and multiplex biochemical measurement then performed on intra- and extracellular signaling molecules. We uncover major differences between primary and transformed hepatocytes with respect to the engagement of toll-like receptor and NF-κBdependent secretion of chemokines and cytokines that prime and attract immune cells. Overall, our results serve as a proof-of-principle for an approach to network analysis that is systematic, comparative and biochemically focused. More specifically, our data support the hypothesis that HCC cells down-regulate normal inflammatory and immune responses to avoid immune editing. National Institutes of Health (U.S.) (Grant GM68762) National Institutes of Health (U.S.) (Grant CA112967) 2013-01-09T21:29:51Z 2013-01-09T21:29:51Z 2010-05 2010-05 Article http://purl.org/eprint/type/JournalArticle 1535-9476 1535-9484 http://hdl.handle.net/1721.1/76231 Alexopoulos, L. G. et al. “Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling Between Normal and Transformed Hepatocytes.” Molecular & Cellular Proteomics 9.9 (2010): 1849–1865. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. en_US http://dx.doi.org/10.1074/mcp.M110.000406 Molecular and Cellular Proteomics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Society for Biochemistry and Molecular Biology (ASBMB) PMC |
| spellingShingle | Alexopoulos, Leonidas G. Rodriguez, Julio Saez Cosgrove, Benjamin D. Lauffenburger, Douglas A. Sorger, Peter K. Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title | Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title_full | Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title_fullStr | Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title_full_unstemmed | Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title_short | Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes |
| title_sort | networks inferred from biochemical data reveal profound differences in toll like receptor and inflammatory signaling between normal and transformed hepatocytes |
| url | http://hdl.handle.net/1721.1/76231 |
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