Dataset Information

Gamma ray irradiation of epithelial carcinoma cells under hypoxic conditions

ABSTRACT: We demonstrate for the first time that under hypoxic conditions, A431 epithelial carcinoma cells exhibit increased viability when exposed to low-dose ?-irradiation, indicating that radiotherapy can promote tumor cell survival when oxygen supply is limited. When assessed using iTRAQ quantitative proteomics and Western blotting, irradiated tumor cells were observed to significantly up-regulate the expression of calcium-binding proteins CALM1, CALU and RCN1, suggesting important roles for these mediators in promoting tumor cell survival during hypoxia.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Newman Sze

PROVIDER: MSV000080784 | MassIVE | Wed Mar 29 14:36:00 BST 2017

SECONDARY ACCESSION(S): PXD003937

REPOSITORIES: MassIVE

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Publications

Irradiation of Epithelial Carcinoma Cells Upregulates Calcium-Binding Proteins That Promote Survival under Hypoxic Conditions.

Ren Yan Y Yeoh Kheng Wei KW Hao Piliang P Kon Oi Lian OL Sze Siu Kwan SK

Journal of proteome research 20161110 12

Hypoxia is thought to promote tumor radio-resistance via effects on gene expression in cancer cells that modulate their metabolism, proliferation, and DNA repair pathways to enhance survival. Here we demonstrate for the first time that under hypoxic condition A431 epithelial carcinoma cells exhibit increased viability when exposed to low-dose γ-irradiation, indicating that radiotherapy can promote tumor cell survival when oxygen supply is limited. When assessed using iTRAQ quantitative proteomic ...[more]

PMID: 27790916

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Project description:Tumor hypoxia is linked to poor outcome for many cancers, but the underlying mechanisms and the environmental factors that initiate tumor hypoxia are poorly understood. Here, we tracked tumor hypoxia in glioblastoma (GBM), a highly malignant brain cancer, in immunocompetent mice with a sensitive fluorescent reporter combined with single cell transcriptomics. We found that hypoxic GBM cells are quiescent and display a mesenchymal transition, both linked to malignant potency. We also captured in vivo hypoxia gene signature, which is more represented in recurrent GBM and predicts worse outcome. Interestingly, hypoxic GBM cells is a diverse population, consisted of four subclusters, and enriched for immune pathways. Concordantly, our reporter highlighted a distinct geographic pattern of immune cells in hypoxic regions, with phagocytic tumor-associated macrophages (TAMs) and CD8+ cytotoxic T cells (CTLs) congregated in hypoxic cores confined by hypoxic GBM cells in pseudopalisading patterns. Mechanistically, this is a dynamic temporospatial process, requiring cytokine CCL8. Remarkably, the sequestered TAMs also experience hypoxia, and they are reprogrammed to an immunotolerant state by factors released from hypoxic GBM cells. Contrary to the conventional viewpoint that hypoxia arises from rapid tumor expansion outstripping vascular supply, we discovered anticancer immunity as an important driving force of tumor hypoxia. Attenuating immune responses by implanting GBM in host mice with immunodeficiency or IL1β deletion significantly decreased GBM hypoxia in well-established tumors. Unexpectedly, radiation therapy (XRT) greatly reduced tumor hypoxia, and when combined with evofosfamide, a prodrug activated by hypoxia, achieved enhanced efficacy in tumor shrinkage and eradication of hypoxic GBM population. Analyses of human patient GBM samples highlighted a connection of mesenchymal subtype, immune response, and tumor hypoxia, all contributing to poor survival. Altogether, our study revealed a reciprocal influence of anti-tumor immunity and tumor hypoxia, which has important ramification for prognosis and immunotherapy for GBM.

Dataset Information

Gamma ray irradiation of epithelial carcinoma cells under hypoxic conditions

Publications

Irradiation of Epithelial Carcinoma Cells Upregulates Calcium-Binding Proteins That Promote Survival under Hypoxic Conditions.

Similar Datasets

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