Unknown,Transcriptomics,Genomics,Proteomics

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Low-power photodynamic therapy induces survival signaling in cultured hilar cholangiocarcinoma cells

ABSTRACT: Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizerreplete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-ÎºB)-, hypoxia-inducible factor 1-alpha (HIF-1Î±)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), and unfolded protein response-mediated pathways). To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following a 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm2). Cells were harvested 90 minutes post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. Hilar cholangiocarcinoma (SK-ChA-1) cells were incubated with PBS (control group) or 500 Î¼M zinc phthalocyanine (ZnPC)-encapsulating liposomes (ZnPC-ITLs, final lipid concentration). After 30 minutes, cells that were incubated with ZnPC-ITLs were either kept in the dark (ITL group) or were treated with 500-mW (ITL 500) or 50-mW (ITL 50) laser light (n = 3 per group, cumulative light dose of 15 J/cm2). Ninety minutes after photodynamic therapy, total cellular RNA was isolated and gene expression levels were analyzed by using the Illumina HumanHT-12 v4 platform. The data was analyzed in the context of survival signalling and comparisons were made with the control group.

ORGANISM(S): Homo sapiens

SUBMITTER: Perry Moerland

PROVIDER: E-GEOD-68292 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells.

Weijer Ruud R Broekgaarden Mans M van Golen Rowan F RF Bulle Esther E Nieuwenhuis Esther E Jongejan Aldo A Moerland Perry D PD van Kampen Antoine H C AH van Gulik Thomas M TM Heger Michal M

BMC cancer 20151226

<h4>Background</h4>Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activatio ...[more]

PMID: 26705830

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Project description:A specialized population of memory CD8+ T-cells resides in the epithelium of the respiratory tract to maintain protection against recurring infections. These cells express CD69 and the integrin Î±Î²7 (CD103) and correspond to tissue resident memory T-cells (TRM) also described in intestine, liver and brain. A less well characterized population of CD103- CD8+ T-cells also resides in lungs and expresses markers characteristic of effector memory T-cells (TEM). We determined the transcriptional profiles of these memory CD8+ T-cell subsets retrieved from human lung resection samples and compared these with corresponding T-cell populations from peripheral blood of the same individuals. Our results demonstrate that each of the populations exhibits a distinct transcriptional identity. We found that the lung environment has a major impact on gene expression profiles. Thus, transcriptomes from CD103+ and CD103- subsets from lungs are much more resemblant to one another than to those from CD103+ or CD103- memory CD8+ T-cells from blood. TRM express specific sets of chemokine receptors, in accordance with their unique migratory properties. Furthermore, these cells constitutively express cytokine and cytotoxic genes for immediate effector function and chemokines to attract auxiliary immune cells. At the same time, multiple genes encoding inhibitory regulators are also expressed. This suggests that rapid ability to unleash effector functions is counterbalanced by programmed restraint, a combination that may be critical in the exposed but delicate tissue of the lung. Comprehensive sets of transcription factors were identified that characterize the memory CD8+ populations in the lungs. Prominent among these were components of the Notch pathway. Using mice genetically lacking expression of the NOTCH1 and NOTCH2 receptors in T-cells, we demonstrated that Notch controls both the number of lung TRM as well as the function of lung TEM. Our data illustrate the adaptation of lung resident T-cells to the requirements of the respiratory epithelial environment. Defining the molecular imprinting of these cells is important for rational vaccine design and may help to improve the properties of T-cells for adoptive cellular therapy. Material was collected from a total of 6 subjects. Three patients underwent a lobectomy for a peripheral primary lung tumor and three received lung transplantation because of end-stage pulmonary disease (COPD). Lung mononuclear cells where isolated after digestion of the partial or complete human lung resection material. Paired peripheral blood mononuclear cells were also isolated. CD8+CD16-CD56- T-cells were sorted for expression of CD103 (ITGAE). Lung and blood derived CD103+ and CD103- T-cell fractions were directly lysed after FACS sorting or stimulated overnight with antiCD3/28 beads. Due to the low frequency of resting (non-stimulated) CD103+ T-cells in peripheral blood this subset was obtained from five non-related buffy coat donors. RNA was isolated from 36 sorted cell samples and hybridized on Illumina HumanHT-12 V4.0 microarrays. Eight microarray samples (including two samples from the buffy coat donors) were excluded after hybridization since their average signal was too low.

Dataset Information

Low-power photodynamic therapy induces survival signaling in cultured hilar cholangiocarcinoma cells

Publications

Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells.

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