Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts
Although hypoxia is known to contribute to several aspects of tumour progression, relatively little is known about the effects of hypoxia on cancer-associated myofibroblasts (CAMs), or the consequences that conditional changes in CAM function may have on tumour development and metastasis. To investi...
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| Veröffentlicht in: | Cancers 2019-02, Vol.11 (2), p.263 |
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| creator | Najgebauer, Hanna Jarnuczak, Andrew F Varro, Andrea Sanderson, Christopher M |
| description | Although hypoxia is known to contribute to several aspects of tumour progression, relatively little is known about the effects of hypoxia on cancer-associated myofibroblasts (CAMs), or the consequences that conditional changes in CAM function may have on tumour development and metastasis. To investigate this issue in the context of gastric cancer, a comparative multiomic analysis was performed on populations of patient-derived myofibroblasts, cultured under normoxic or hypoxic conditions. Data from this study reveal a novel set of CAM-specific hypoxia-induced changes in gene expression and secreted proteins. Significantly, these signatures are not observed in either patient matched adjacent tissue myofibroblasts (ATMs) or non-cancer associated normal tissue myofibroblasts (NTMs). Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts. |
| doi_str_mv | 10.3390/cancers11020263 |
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To investigate this issue in the context of gastric cancer, a comparative multiomic analysis was performed on populations of patient-derived myofibroblasts, cultured under normoxic or hypoxic conditions. Data from this study reveal a novel set of CAM-specific hypoxia-induced changes in gene expression and secreted proteins. Significantly, these signatures are not observed in either patient matched adjacent tissue myofibroblasts (ATMs) or non-cancer associated normal tissue myofibroblasts (NTMs). Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers11020263</identifier><identifier>PMID: 30813438</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Cell adhesion & migration ; Cell growth ; Cell migration ; DNA methylation ; Extracellular matrix ; Fibroblasts ; Gastric cancer ; Gene expression ; Growth factors ; Hypoxia ; Medical prognosis ; Metastases ; Metastasis ; Oxidative stress ; Proteins ; Tumors</subject><ispartof>Cancers, 2019-02, Vol.11 (2), p.263</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 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Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts.</description><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>DNA methylation</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Hypoxia</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Oxidative stress</subject><subject>Proteins</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctLJDEQxsOirKKe97YEvHiZNZV0J92XBRl8DLgoPs6hJp3MRnqSMekenP9-4xPXXCpQv_qorz5CfgD7JUTLjg0GY1MGYJxxKb6RXc4Un0jZVluf_jvkIOcHVp4QoKT6TnYEa0BUotklq1kY7CLh4NeWXi29odcpOt_7sKA3dm2xz_Q--MfR0ovNKj55pLPQjcZ29NYvAg5jspn6QM8xD6mMT1-Woic5R-NxKNyfTRGcpzjvC5L3ybYrovbgre6R-7PTu-nF5PLqfDY9uZyYisMwgY4pBIe2QwAlDAonHcwbaSV3CtuqxloJJWTdubo1wqmqbaxzDMA5CVLskd-vuqtxvrSdsWFI2OtV8ktMGx3R6_87wf_Vi7jWsmLlas8CR28CKRb7edBLn43teww2jllzaBTjFYO6oIdf0Ic4plDsaV5XqmZCtapQx6-USTHnZN3HMsD0c6D6S6Bl4udnDx_8e3ziHylFn1M</recordid><startdate>20190223</startdate><enddate>20190223</enddate><creator>Najgebauer, Hanna</creator><creator>Jarnuczak, Andrew F</creator><creator>Varro, Andrea</creator><creator>Sanderson, Christopher M</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1010-0403</orcidid><orcidid>https://orcid.org/0000-0001-6368-3951</orcidid></search><sort><creationdate>20190223</creationdate><title>Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts</title><author>Najgebauer, Hanna ; 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| subjects | Cell adhesion & migration Cell growth Cell migration DNA methylation Extracellular matrix Fibroblasts Gastric cancer Gene expression Growth factors Hypoxia Medical prognosis Metastases Metastasis Oxidative stress Proteins Tumors |
| title | Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts |
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