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Cancers 2019, 11(2), 263; https://doi.org/10.3390/cancers11020263

Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts

1
Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK
2
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
*
Author to whom correspondence should be addressed.
Received: 30 January 2019 / Revised: 15 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract

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. View Full-Text
Keywords: cancer-associated myofibroblasts; hypoxia; tumour microenvironment; gene expression; secretome; transcriptomics; proteomics; gastric cancer; omics cancer-associated myofibroblasts; hypoxia; tumour microenvironment; gene expression; secretome; transcriptomics; proteomics; gastric cancer; omics
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Najgebauer, H.; Jarnuczak, A.F.; Varro, A.; Sanderson, C.M. Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts. Cancers 2019, 11, 263.

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